RESUMO
BACKGROUND: Many studies have described barriers to gender-affirming surgery (GAS) in Canada; however, few have explored why these barriers persist. To address this knowledge gap, we sought to describe documents related to public health insurance (Medicare) for GAS to identify the types of procedures covered, variations in coverage across provinces and territories, and changes in policy over time. METHODS: We conducted a descriptive cross-sectional study using an environmental scan approach. We queried 23 government websites, the Google search engine, and an online legal database between July 2022 and April 2024 to gather gray literature documents related to GAS and Medicare. Variables from relevant documents were compiled to create a present, at-glance overview of GAS Medicare coverage for all provinces and territories and a timeline of policy changes across Canada. RESULTS: Eight provinces and three territories had documents or websites related to GAS Medicare coverage (85%). We identified 15 GAS procedures that were covered variably across Canada. Yukon (n = 14) covered the most types of GAS, while Quebec and Saskatchewan covered the least (n = 6). Mastectomy and genital surgeries were covered across Canada, but other GAS were rarely covered. Five provinces and territories provided coverage for travel-related costs. Our GAS Medicare timeline showed differential expansion of GAS coverage in Canada over the last 25 years. CONCLUSIONS : We provide previously unreported information regarding GAS Medicare coverage in Canada. We hope our findings will help patients and healthcare providers navigate a complicated public healthcare system. We also highlight barriers within GAS Medicare documents and make recommendations to alleviate those barriers.
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Cirurgia de Readequação Sexual , Humanos , Canadá , Estudos Transversais , Feminino , Cirurgia de Readequação Sexual/economia , Masculino , Política de Saúde , Programas Nacionais de Saúde , Medicare/economia , Cobertura do Seguro/estatística & dados numéricosRESUMO
PURPOSE OF REVIEW: Schizophrenia spectrum disorders (SSD) impact many aspects of reproductive health for women and non-binary and transgender individuals assigned female at birth. In this narrative review, we highlight considerations and recent research related to (1) the premenopausal period, (2) pregnancy and postpartum, and (3) the menopausal transition. RECENT FINDINGS: Most recent research has focused on pregnancy and the postpartum period, and specifically on elucidating perinatal risk factors, adverse obstetrical and neonatal outcomes (and modifiable contributors such as smoking), long-term child health, and psychotropic medications (with reassuring results related antipsychotic-associated gestational diabetes mellitus and neurodevelopmental outcomes). Much less recent focus has been on menstruation and menopause, although some research has highlighted the relative worsening of illness peri-menstrually and peri-menopausally. Despite the many important reproductive considerations for those with SSD, many aspects including menstruation and menopause have received very little attention. Further research is needed on how to best support women, non-binary, and transgender people assigned female at birth with SSD throughout the lifespan.
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Esquizofrenia , Gravidez , Recém-Nascido , Criança , Feminino , Humanos , Pré-Menopausa , Saúde Reprodutiva , Menopausa , Período Pós-PartoRESUMO
IMPORTANCE: Vaginoplasty is a relatively common gender-affirming surgery with approximately 200 Ontarians seeking this surgery annually. Although Ontario now offers vaginoplasty in province, the capacity is not meeting demand; the majority of trans and gender-diverse patients continue to seek vaginoplasty out of province. Out-of-province surgery presents a barrier to accessing postsurgical follow-up care leaving most patients to seek support from their primary care providers or providers with little experience in gender-affirming surgery. OBJECTIVE: To provide an account of the common postoperative care needs and neovaginal concerns of Ontarians who underwent penile inversion vaginoplasty out of province and presented for care at a gender-affirming surgery postoperative care clinic. DESIGN, SETTINGS, AND PARTICIPANTS: A retrospective chart review of the first 80 patients presenting to a gender-affirming surgery postoperative care clinic who had undergone vaginoplasty at an outside surgical center was performed. Descriptive analyses were performed for all variables. RESULTS: The sample consisted of 80 individuals with the mean age of 39 years (19-73). Most patients had surgery at another surgical center in Canada (76.3%). Many patients (22.5%) accessed care in the first 3 months after surgery, with the majority (55%) seeking care within the first perioperative year. Most patients (61.3%) were seen for more than one visit and presented with more than two symptoms or concerns. Common patient-reported symptoms during clinical visit included pain (53.8%), dilation concerns (46.3%), and surgical site/vaginal bleeding (42.5%). Sexual function concerns were also common (33.8%) with anorgasmia (11.3%) and dyspareunia (11.3%) being the most frequent complications. The most common adverse outcomes identified by health care providers included hypergranulation (38.8%), urinary dysfunction (18.8%), and wound healing issues (12.5%). CONCLUSIONS AND RELEVANCE: Findings from chart review offer valuable insights into the postoperative needs and neovaginal concerns of Ontarians who have had vaginoplasty out of province. This study demonstrates the need for routine postoperative care in patients undergoing vaginoplasty. Patients experience numerous symptoms and concerns that often correlate with clinical findings and require multiple follow-up appointments. Health care providers may benefit from further education on the more common nonsurgical issues identified in this study.
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Pessoas Transgênero , Masculino , Feminino , Humanos , Adulto , Estudos Retrospectivos , Cuidados Pós-Operatórios , Vagina/cirurgia , Medidas de Resultados Relatados pelo Paciente , Ontário/epidemiologiaRESUMO
BACKGROUND: Congenital cataracts are lens opacities in one or both eyes of babies or children present at birth. These may cause a reduction in vision severe enough to require surgery. Cataracts are proportionally the most treatable cause of visual loss in childhood, and are a particular problem in low-income countries, where early intervention may not be possible. Paediatric cataracts provide different challenges to those in adults. Intense inflammation, amblyopia (vision is obstructed by cataract from birth which prevents normal development of the visual system), posterior capsule opacification and uncertainty about the final trajectory of ocular growth parameters can affect results of treatment. Two options currently considered for children under 2 years of age with bilateral congenital cataracts are: (i) intraocular lens (IOL) implantation; or (ii) leaving a child with primary aphakia (no lens in the eye), necessitating the need for contact lenses or aphakic glasses. Other important considerations regarding surgery include the prevention of visual axis opacification (VAO), glaucoma and the route used to perform lensectomy. OBJECTIVES: To assess the effectiveness of infant cataract surgery or lensectomy to no surgery for bilateral congenital cataracts in children aged 2 years and under. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 1); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 25 January 2022. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared infant cataract surgery or lensectomy to no surgery, in children with bilateral congenital cataracts aged 2 years and younger. This update (of a review published in 2001 and updated in 2006) does not include children over 2 years of age because they have a wider variety of aetiologies, and are therefore managed differently, and have contrasting outcomes. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. Two review authors extracted data independently. We assessed the risk of bias of included studies using RoB 1 and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We identified three RCTs that met our inclusion criteria with each trial comparing a different aspect of surgical intervention for this condition. The trials included a total of 79 participants under 2 years of age, were conducted in India and follow-up ranged from 1 to 5 years. Study participants and outcome assessors were not masked in these trials. One study (60 children) compared primary IOL implantation with primary aphakia. The results from this study suggest that there may be little or no difference in visual acuity at 5 years comparing children with pseudophakia (mean logMAR 0.50) and aphakia (mean logMAR 0.59) (mean difference (MD) -0.09 logMAR, 95% confidence intervals (CIs) -0.24 to 0.06; 54 participants; very low-certainty evidence), but the evidence is very uncertain. The evidence is very uncertain as to the effect of IOL implantation compared with aphakia on visual axis opacification (VAO) (risk ratio (RR) 1.29, 95% CI 0.23 to 7.13; 54 participants; very low-certainty evidence). The trial investigators did not report on the cases of amblyopia. There was little evidence of a difference betwen the two groups in cases of glaucoma at 5 years follow-up (RR 0.86, 95% CI 0.24 to 3.10; 54 participants; very low-certainty evidence). Cases of retinal detachment and reoperation rates were not reported. The impact of IOL implantation on adverse effects is very uncertain because of the sparse data available: of the children who were pseudophakic, 1/29 needed a trabeculectomy and 8/29 developed posterior synechiae. In comparison, no trabeculectomies were needed in the aphakic group and 2/25 children had posterior synechiae (54 participants; very low-certainty evidence). The second study (14 eyes of 7 children under 2 years of age) compared posterior optic capture of IOL without vitrectomy versus endocapsular implantations with anterior vitrectomy (commonly called 'in-the-bag surgery'). The authors did not report on visual acuity, amblyopia, glaucoma and reoperation rate. They had no cases of VAO in either group. The evidence is very uncertain as to the effect of in-the-bag implantation in children aged under 1 year. There was a higher incidence of inflammatory sequelae: 4/7 in-the-bag implantation eyes and 1/7 in optic capture eyes (P = 0.04, 7 participants; very low-certainty evidence). We graded the certainty of evidence as low or very low for imprecision in all outcomes because their statistical analysis reported that a sample size of 13 was needed in each group to achieve a power of 80%, whereas their subset of children under the age of 1 year had only 7 eyes in each group. The third study (24 eyes of 12 children) compared a transcorneal versus pars plana route using a 25-gauge transconjunctival sutureless vitrectomy system. The evidence is very uncertain as to the effect of the route chosen on the incidence of VAO, with no cases reported at 1 year follow-up in either group. The investigators did not report on visual acuity, amblyopia, glaucoma, retinal detachment and reoperation rate. The pars plana route had the adverse effects of posterior capsule rupture in 2/12 eyes, and 1/12 eyes needing sutures. Conversely, 1/12 eyes operated on by the transcorneal route needed sutures. We graded the outcomes with very low-certainty because of the small sample size and the absence of a priori sample size calculation. AUTHORS' CONCLUSIONS: There is no high level evidence for the effectiveness of one type of surgery for bilateral congenital cataracts over another, or whether surgery itself is better than primary aphakia. Further RCTs are required to inform modern practice about concerns, including the timing of surgery, age at which surgery should be undertaken, age for implantation of an IOL and development of complications, such as reoperations, glaucoma and retinal detachment. Standardising the methods used to measure visual function, along with objective monitoring of compliance with the use of aphakic glasses/contact lenses would greatly improve the quality of study data and enable more reliable interpretation of outcomes.
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Ambliopia , Afacia , Opacificação da Cápsula , Glaucoma , Descolamento Retiniano , Ambliopia/etiologia , Ambliopia/prevenção & controle , Ambliopia/cirurgia , Afacia/etiologia , Opacificação da Cápsula/etiologia , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Implante de Lente Intraocular/métodos , Descolamento Retiniano/etiologiaRESUMO
BACKGROUND: The World Health Organization recommends mothers and infants be in direct skin-to-skin contact immediately after birth and initiate breastfeeding as soon as possible. Little is known in women with schizophrenia. METHODS: We conducted a population-based cohort study using administrative health data from Ontario, Canada (2012-2014), comparing women with (n = 471) and without schizophrenia (n = 218 435), and their infants, on the primary outcomes of any skin-to-skin contact and opportunity to initiate breastfeeding within the first 2 h after birth. For dyads with available data, secondary outcomes of intention to breastfeed, breastfeeding support, any breastmilk, and exclusive breastmilk at discharge were assessed. Modified Poisson regression was used to generate relative risks (aRR) and 95% confidence intervals (CI), adjusted for maternal age, parity, neighbourhood income, region of residence, smoking in pregnancy, and maternal medical and non-psychotic psychiatric comorbidity for all outcomes. RESULTS: Maternal schizophrenia was associated with lower likelihood of skin-to-skin contact (65.2% vs 78.1%; aRR 0.88, 95% CI: 0.82-0.94), and breastfeeding initiation post-delivery (38.9% vs 52.6% aRR 0.80, CI: 0.71-0.90) compared to dyads unexposed to maternal schizophrenia. Secondary outcomes followed a similar pattern. The magnitude of the effect was slightly less when restricting the cohort to full-term, vaginal deliveries, not admitted to NICU, and infant not discharged to social services. CONCLUSIONS: Reduced maternal-infant skin-to-skin contact and breastfeeding initiation immediately after birth may significantly impact maternal-child bonding and the establishment breastfeeding in this population. Mothers with schizophrenia may require individualized support to promote these WHO recommended hospital practices in the early post-natal period.
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Aleitamento Materno/estatística & dados numéricos , Filho de Pais com Deficiência/estatística & dados numéricos , Parto Obstétrico/estatística & dados numéricos , Relações Mãe-Filho , Apego ao Objeto , Esquizofrenia/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Ontário/epidemiologia , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Serum bile acids (SBAs) are frequently measured in dogs. However, there is limited data comparing SBAs in different liver diseases diagnosed according to standardized histological criteria. OBJECTIVES: To compare resting and postprandial SBAs, and determine their sensitivity and specificity, for various liver diseases in dogs. ANIMALS: Three hundred and forty-one client-owned dogs with suspected liver disease that had a liver biopsy and SBAs measured. METHODS: Multicenter retrospective study. Cases were classified according to standardized histological criteria. The sensitivity and specificity of resting and postprandial SBAs for the diagnosis of each liver disease, and all liver diseases combined, were calculated. RESULTS: The median resting SBAs were highest in dogs with cirrhosis (98.8 µmol/L; range, 6-135) and congenital circulatory anomalies (CCa; 79.45 µmol/L; 0.3-705). The highest median postprandial concentrations were found in CCa (126 µmol/L; 0-726) and chronic hepatitis (CH; 54.3 µmol/L; 0-260). Using the cut-off value of 10 µmol/L, the highest sensitivities of resting SBAs were recorded in dogs with CCa (87.5%; 95% confidence interval, 76.8-94.4) and CH (81.1%; 71.5-88.6). The sensitivities of postprandial SBAs were the highest in cholangitis (100%; 47.8-100.0) and CCa (91.1%; 78.8-97.5). The specificities of resting and postprandial SBAs for all diseases were 49.3% (37.6-61.1) and 29.7% (15.9-47.0), respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Postprandial SBAs are more sensitive but less specific than resting SBAs for the diagnosis of liver disease. There were dogs in all categories of liver disease with resting SBAs <10 and >90 µmol/L. Therefore, careful interpretation of both normal and elevated values is required.
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Doenças do Cão , Hepatopatias , Animais , Ácidos e Sais Biliares , Doenças do Cão/diagnóstico , Cães , Cirrose Hepática/veterinária , Hepatopatias/veterinária , Estudos RetrospectivosRESUMO
PURPOSE: Maternal schizophrenia is associated with adverse birth outcomes, but the reasons for this remain unclear. In a population-based cohort of infants born to women with schizophrenia, we determined the occurrence of key perinatal outcomes and explored whether factors identifiable in our datasets explained any elevated risk. METHODS: Using population-level health administrative data linked to clinical birth-registry data in Ontario, Canada (2006-2011), we examined the relative risk (RR) of preterm birth (< 37 weeks), small for gestational age (SGA), and Apgar scores < 8 in infants of women with schizophrenia (n = 4279) versus infants of unaffected women (n = 286,147). Generalized estimating equations determined whether reproductive history, maternal health conditions, pregnancy exposures, and complications explained elevated RRs. RESULTS: Among infants of women with schizophrenia, risk was higher for prematurity (11.4% vs. 6.9%, aRR 1.64, 95% CI 1.51-1.79), SGA (3.5% vs. 2.5%, aRR 1.40, 95% CI 1.20-1.64), and Apgar score < 8 at 1 (19.0% vs. 12.8%, aRR 1.49, 95% CI 1.40-1.59) and 5 min (5.6% vs. 3.0%, aRR 1.90, 95% CI 1.68-2.16). Smoking, fourfold more common among women with schizophrenia, was the variable that explained the greatest proportion of the elevated aRR for prematurity (9.9%), SGA (28.7%), and Apgar < 8 at 1 and 5 min (9.8%, 5.6%). Illicit substance use, certain reproductive history variables, and pregnancy complications also contributed to the elevated aRR for preterm birth. CONCLUSIONS: Elevated risks of preterm birth, SGA, and low Apgar scores in infants of women with schizophrenia are partly explained by potentially modifiable factors such as smoking and illicit drug use, suggesting opportunities for targeted intervention.
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Complicações na Gravidez/terapia , Esquizofrenia/terapia , Adolescente , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Pessoa de Meia-Idade , Ontário , Gravidez , Resultado da Gravidez , Nascimento Prematuro , Fatores de Risco , Adulto JovemRESUMO
INTRODUCTION: Vertical deviations in thyroid eye disease (TED) can present a surgical challenge due to the difficulty and unpredictability of surgery and the high risk of postoperative drift towards overcorrection. This study reports the postoperative outcomes of patients who underwent adjustable vertical strabismus surgery with Vicryl sutures for thyroid eye disease. METHODS: We reviewed the records of patients seen for vertical TED strabismus surgery from January 2005 through December 2009. Clinical details were recorded preoperatively, post-adjustment, and at 3 weeks, 3 months, and 1 year postoperatively. RESULTS: The study included 42 patients. Mean age was 62.4 years and 70% were female. All patients were diplopic preoperatively. The mean near vertical deviation was 21.1 prism diopters (PD) preoperatively, 4.0 PD at 3 weeks postoperatively, 5.0 PD at 3 months, and 4.4 PD at 1 year (all mean results representing undercorrection). 71.4% were free of diplopia postoperatively. Seven patients required further surgery, 2 patients needed further botulinum toxin A. Eight patients experienced an overcorrection; five at 3 weeks, seven at 3 months, and eight at 1 year. There was a significant difference in the mean near angle at tie-off post-adjustment in the patients that overcorrected compared to those that did not reverse (3.1 PD vs 7.1 PD; P=0.005). DISCUSSION: Adjustable surgery for vertical strabismus in thyroid eye disease may result in late overcorrection and the need for further intervention. We propose that aiming for an immediate post-adjustment angle of 8 PD undercorrection for near would allow for postoperative drift and reduce the chances of a late overcorrection. This would require careful preoperative counseling of the patient in order to explain that immediate undercorrection and persistent diplopia were necessary in order to generate a better long-term result.
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Diplopia/fisiopatologia , Oftalmopatia de Graves/cirurgia , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Estrabismo/cirurgia , Feminino , Seguimentos , Oftalmopatia de Graves/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estrabismo/fisiopatologia , Técnicas de Sutura , Resultado do TratamentoRESUMO
PURPOSE: To assess the incidence, duration, and severity of oscillopsia after lateral wall orbital decompression for thyroid eye disease. DESIGN: Retrospective telephone interview. PARTICIPANTS: A consecutive group of patients who had undergone lateral wall orbital decompression for thyroid eye disease performed by 2 consultants at Moorfields Eye Hospital between January 2008 and December 2010. METHODS: Patients were telephoned and a standardized interview related to postoperative oscillopsia was performed. The degree of preoperative and late postoperative exophthalmometry was assessed from clinical records. MAIN OUTCOME MEASURES: The presence, severity, and duration of postoperative oscillopsia and its impact on daily activities. RESULTS: Ninety-eight patients were interviewed successfully, of which 34 (35%) had noted postoperative oscillopsia that occurred upon chewing in 29 of 34 patients (85%) and upon walking in 8 of 34 patients (24%). The oscillopsia resolved within 1 year in 15 of 34 patients (44%), and 16 of 34 (47%) still had mild symptoms at 2 years or more after surgery. Fourteen patients (41% of affected patients; 14% of the entire group) initially were troubled by the symptom, but at the time of interview, only 1 person found it troublesome and 7 reported it as a minimal problem. The reduction in proptosis was similar among those with and without oscillopsia. CONCLUSIONS: The incidence of oscillopsia after lateral wall orbital decompression was 35% when patients were questioned directly, and was much higher than anticipated from extensive clinical experience (where very few patients mention the symptom). In almost all cases, the oscillopsia resolved or was not troublesome, and only 1 patient found it bothersome more than 2 years after surgery. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Descompressão Cirúrgica/efeitos adversos , Oftalmopatia de Graves/cirurgia , Órbita/cirurgia , Transtornos da Visão/etiologia , Atividades Cotidianas , Adulto , Idoso , Feminino , Oftalmopatia de Graves/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Órbita/diagnóstico por imagem , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Forehead paresthesia after brow lift is well-documented with rates as high as 40.7%. The authors describe an anatomical study to identify the variation in position of the supraorbital notch/foramen to define safe limits for deep dissection during this procedure. METHODS: Sixty-six orbits from 23 dry skulls and 9 formalin-fixed cadavers were analyzed photographically using ImageJ software. The cadaveric specimens were dissected using a coronal incision, which allowed the inferior resection of the frontalis muscle and periosteum. The exit point of the supraorbital neurovascular bundle was noted as a foramen or notch. The position of the supraorbital notch or foramen was recorded in relation to the midline as defined by the sagittal suture at the level of the highest point of the supraorbital rim. The distance and angle for each foramen/notch were calculated. RESULTS: Thirty-three percent of orbits had a foramen. The average distance from the midpoint to the foramen was 25.24 mm (standard deviation 3.78 mm) and to the notch was 22.69 mm (22.69 mm). The range of distance between the midpoint and the foramen/notch was 17.62 to 32.35 mm. The average angle between the horizontal meridian and the foramen was 81/57° (standard deviation 4.69°). CONCLUSIONS: A wide variation in anatomy was seen. Greater caution is required when performing deep dissection around the supraorbital notch because of the variation in position of the supraorbital foramen.
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Sobrancelhas , Testa/cirurgia , Osso Frontal/cirurgia , Órbita/anatomia & histologia , Ritidoplastia/métodos , Idoso , Idoso de 80 Anos ou mais , Cadáver , Cefalometria , Suturas Cranianas/cirurgia , Músculos Faciais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Periósteo/cirurgia , Crânio/cirurgiaRESUMO
Mutations in the bone morphogenetic protein (BMP) type II receptor (BMPR-II) underlie most cases of heritable pulmonary arterial hypertension (HPAH) and a significant proportion of sporadic cases. Pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) not only exhibit attenuated growth suppression by BMPs, but an abnormal mitogenic response to transforming growth factor (TGF)-ß1. We sought to define the mechanism underlying this loss of the antiproliferative effects of TGF-ß1 in BMPR-II-deficient PASMCs. The effect of TGF-ß1 on PASMC proliferation was characterized in three different models of BMPR-II dysfunction: 1) HPAH PASMCs, 2) Bmpr2(+/-) mouse PASMCs, and 3) control human PASMCs transfected with BMPR-II small interfering RNA. BMPR-II reduction consistently conferred insensitivity to growth inhibition by TGF-ß1. This was not associated with altered canonical TGF-ß1/Smad signaling but was associated with a secreted factor. Microarray analysis revealed that the transcriptional responses to TGF-ß1 differed between control and HPAH PASMCs, particularly regarding genes associated with interleukins and inflammation. HPAH PASMCs exhibited enhanced IL-6 and IL-8 induction by TGF-ß1, an effect reversed by NF-κB inhibition. Moreover, neutralizing antibodies to IL-6 or IL-8 restored the antiproliferative effect of TGF-ß1 in HPAH PASMCs. This study establishes that BMPR-II deficiency leads to failed growth suppression by TGF-ß1 in PASMCs. This effect is Smad-independent but is associated with inappropriately altered NF-κB signaling and enhanced induction of IL-6 and IL-8 expression. Our study provides a rationale to test anti-interleukin therapies as an intervention to neutralize this inappropriate response and restore the antiproliferative response to TGF-ß1.
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Receptores de Proteínas Morfogenéticas Ósseas Tipo II/deficiência , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Processos de Crescimento Celular/fisiologia , Células Cultivadas , Hipertensão Pulmonar Primária Familiar , Expressão Gênica , Humanos , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-8/antagonistas & inibidores , Interleucina-8/genética , Camundongos , NF-kappa B/metabolismo , RNA Interferente Pequeno/genética , Proteínas Smad/metabolismo , Transfecção/métodosRESUMO
BACKGROUND: Inflammation is a feature of pulmonary arterial hypertension (PAH), and increased circulating levels of cytokines are reported in patients with PAH. However, to date, no information exists on the significance of elevated cytokines or their potential as biomarkers. We sought to determine the levels of a range of cytokines in PAH and to examine their impact on survival and relationship to hemodynamic indexes. METHODS AND RESULTS: We measured levels of serum cytokines (tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta, -2, -4, -5, -6, -8, -10, -12p70, and -13) using ELISAs in idiopathic and heritable PAH patients (n=60). Concurrent clinical data included hemodynamics, 6-minute walk distance, and survival time from sampling to death or transplantation. Healthy volunteers served as control subjects (n=21). PAH patients had significantly higher levels of interleukin-1beta, -2, -4, -6, -8, -10, and -12p70 and tumor necrosis factor-alpha compared with healthy control subjects. Kaplan-Meier analysis showed that levels of interleukin-6, 8, 10, and 12p70 predicted survival in patients. For example, 5-year survival with interleukin-6 levels of >9 pg/mL was 30% compared with 63% for patients with levels < or = 9 pg/mL (P=0.008). In this PAH cohort, cytokine levels were superior to traditional markers of prognosis such as 6-minute walk distance and hemodynamics. CONCLUSIONS: This study illustrates dysregulation of a broad range of inflammatory mediators in idiopathic and familial PAH and demonstrates that cytokine levels have a previously unrecognized impact on patient survival. They may prove to be useful biomarkers and provide insight into the contribution of inflammation in PAH.
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Biomarcadores/sangue , Citocinas/sangue , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/mortalidade , Inflamação/diagnóstico , Inflamação/mortalidade , Adulto , Idoso , Pressão Sanguínea , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Feminino , Predisposição Genética para Doença , Humanos , Hipertensão Pulmonar/genética , Inflamação/genética , Mediadores da Inflamação/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Resistência VascularRESUMO
A series of novel corticosteroid derivatives featuring C-17 furoate ester functionality have been synthesised. Profiling in vitro and in vivo has resulted in the identification of a compound with a longer duration of action and a lower oral side effect profile in rodents compared to budesonide.