RESUMO
INTRODUCTION: Lichen planopilaris (LPP) is a common type of primary cicatricial alopecia. Previous studies focused on the epidemiology, clinical characteristics, and treatment of LPP. A lack of knowledge regarding LPP outcomes and prognostic factors remained. METHODS: To delineate the rate and timing of remission in LPP, as well as the prognostic factors for achieving remission, a retrospective cohort study was conducted. The study included 126 patients, from a single tertiary center, diagnosed with LPP between January 2010 and December 2022, who were followed up for a minimum of 6 months. RESULTS: There were 89 (70.6%) women and 37 (29.4%) men included in this study. The mean age of the patients was 47.92 ± 14.2 years. The mean time from disease onset to diagnosis was 33.85 (±30) months, indicating significant diagnostic delays. The mean duration of follow-up was 34.13 ± 22.7 months. Among the cohort, 43 patients achieved complete remission (CR) during the follow-up period, whereas 83 patients did not. Of the 83 patients who did not achieve CR, 35 partially improved and 48 did not improve or worsened. The median time for achieving CR was 46 ± 18.8 months. Milder disease at presentation and comorbid lichen planus were associated with higher CR rates. CONCLUSION: This study demonstrates significant diagnostic delays that should be addressed as LPP causes irreversible alopecia, suggests disease severity and comorbid lichen planus as potential prognostic factors. Further, it emphasizes the limited efficacy of current treatments and the need for prolonged treatment in patients with LPP to achieve remission.
Assuntos
Alopecia , Líquen Plano , Indução de Remissão , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Líquen Plano/epidemiologia , Líquen Plano/tratamento farmacológico , Líquen Plano/complicações , Prognóstico , Adulto , IdosoRESUMO
BACKGROUND: Risankizumab has demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis in randomized clinical trials. OBJECTIVES: To evaluate safety data from risankizumab psoriasis phase I-III clinical trials. METHODS: Short-term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long-term safety was evaluated using integrated data from 17 phase I-III completed and ongoing trials. RESULTS: Short-term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient-years (PY) of exposure, respectively]. Long-term analyses included 3072 risankizumab-treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure-adjusted adverse event rates did not increase with long-term treatment (318 vs. 171 events per 100 PY for short- and long-term analyses). With long-term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients. CONCLUSIONS: Risankizumab demonstrated a favourable safety profile over short- and long-term treatment in patients with moderate-to-severe psoriasis.
Assuntos
Anticorpos Monoclonais , Psoríase , Anticorpos Monoclonais/efeitos adversos , Ensaios Clínicos como Assunto , Humanos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Risankizumab has demonstrated durable, high rates of efficacy in patients with moderate-to-severe plaque psoriasis as assessed by the achievement of relative Psoriasis Area and Severity Index (PASI) improvement and Dermatology Life Quality Index (DLQI) 0/1. OBJECTIVES: The aim of this post hoc analysis is to assess the achievement of absolute PASI thresholds and related improvements in health-related quality of life (HRQoL) in patients with moderate-to-severe plaque psoriasis treated with (i) risankizumab compared with ustekinumab, and (ii) long-term (>52 weeks to 172 weeks) risankizumab. METHODS: Data from patients randomised to 150 mg risankizumab or 45 or 90 mg ustekinumab in replicate randomised controlled trials UltIMMa-1 and UltIMMa-2 were analysed for the achievement of absolute PASI thresholds PASI ≤ 3, PASI ≤ 1, and PASI = 0, time to achieve these thresholds, and combined PASI and DLQI endpoints. Data from pat ients initially randomised to risankizumab who continued on risankizumab in the open-label extension study LIMMitless were analysed for the achievement of absolute PASI levels, mean DLQI scores, and DLQI 0/1. RESULTS: Significantly greater proportions of patients treated with risankizumab compared with ustekinumab achieved PASI ≤ 3, PASI ≤ 1, and PASI = 0, as well as combined endpoints for absolute PASI and DLQI [(PASI ≤ 3 and DLQI ≤ 5) or (PASI ≤ 1 and DLQI 0/1)]. The median time to first achieve PASI ≤ 3, PASI ≤ 1, and PASI = 0 was significantly lower for risankizumab-treated patients compared with ustekinumab-treated patients. Among patients treated with long-term risankizumab, more than 90% achieved PASI ≤ 3 though week 172 and more than 80% achieved DLQI 0/1. Low absolute PASI scores corresponded with low mean absolute DLQI scores through week 172 of continuous risankizumab treatment. CONCLUSIONS: Risankizumab treatment demonstrated high rates of rapid and durable efficacy as measured by absolute PASI thresholds and improvements in patient HRQoL.
Assuntos
Psoríase , Ustekinumab , Anticorpos Monoclonais , Humanos , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/uso terapêuticoRESUMO
PURPOSE: To determine whether gestational carrier (GC) in vitro fertilization (IVF) cycles (commissioned cycles) for same-sex or single male intended parents have an increased incidence of adverse perinatal outcomes compared with spontaneous cycles in the same GCs. DESIGN: GC singleton pregnancies were identified from a database of 895 commissioned cycles from a large fertility center. Of these, 78 commissioned cycles met inclusion and exclusion criteria and were compared with 71 spontaneous cycles by the same GCs. The primary outcome was the composite score for adverse perinatal outcomes. Secondary outcomes included mode of delivery, birthweight, and gestational age. Chi-square test of association and Mann-Whitney U tests were used to compare categorical and continuous variables between the cohorts, respectively. Logistic and linear regressions controlling for GC age were constructed to determine the influence of GC cycle type on adverse perinatal outcomes. RESULTS: Commissioned cycles were significantly associated with adverse perinatal outcomes (25.6% vs. 9.9%; p = 0.02) and lower average gestational age (38.7 ± 1.5 vs. 39.4 ± 0.9; p < 0.001) compared with spontaneous cycles. Commissioned cycle increased the likelihood of adverse perinatal outcomes (OR 3.3; p = 0.03) and was a significant independent predictor of a lower average gestational age (ß = 0.897; p < 0.001). There were no significant differences in the incidence of vaginal deliveries or cesarean sections between commissioned and spontaneous cycles. CONCLUSIONS: Commissioned cycles confer a greater incidence of composite perinatal complications and were independently associated with a lower average gestational age when compared with spontaneous pregnancies carried by the same GC despite a confirmed healthy uterine environment, sperm samples, and donor oocytes.
Assuntos
Fertilidade/fisiologia , Fertilização in vitro , Resultado da Gravidez , Mães Substitutas , Adulto , Peso ao Nascer , Cesárea , Transferência Embrionária , Feminino , Fertilidade/genética , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Casamento , Indução da Ovulação/métodos , Assistência Perinatal , Gravidez , Nascimento Prematuro , Estudos Retrospectivos , Transferência de Embrião ÚnicoRESUMO
OBJECTIVES: Nationally representative studies suggest 1-2% of Indonesian women (2.3 million) smoke various tobacco products daily; however, in recent years, there has been concern that the tobacco industry has successfully increased female smoking. Our objective was to describe current cigarette smoking behaviors, past quit attempts, and intention to quit of female daily smokers in Surabaya, Indonesia. STUDY DESIGN: Survey. METHODS: Female daily smokers (n = 112) in Surabaya, Indonesia, the country's second largest city, were recruited to participate in a survey during 2018. Convenience sampling was utilized in two malls. Potential participants were intercepted in or near designated smoking areas and invited to the nearby data collection site. Survey items from Global Adult Tobacco Survey and the International Tobacco Control Policy Evaluation Project were utilized. RESULTS: Participants self-reported smoking 13.8 cigarettes per day (7.3 white machine-rolled cigarettes per day, 4.2 kreteks per day, and 2.4 roll-your-own cigarettes per day). Over 75% smoked their first cigarette within 30 min of waking. Over 53% had a heaviness of smoking index score suggesting moderate or high addiction. Approximately half (51%) did not attempt to quit smoking in the previous 12 months, and 55% planned to quit beyond 6 months or not at all. CONCLUSIONS: Our sample smoked five to six more cigarettes per day than female daily smokers in previous national surveys. Relative to previous studies, our data suggest an unexpected preference for white machine-rolled cigarettes and that there could be, at a minimum, pockets of increased smoking and addiction among female daily smokers in Indonesia.
Assuntos
Fumar Cigarros/psicologia , Intenção , Fumantes/psicologia , Abandono do Hábito de Fumar/psicologia , Adolescente , Adulto , Fumar Cigarros/epidemiologia , Feminino , Humanos , Indonésia/epidemiologia , Fumantes/estatística & dados numéricos , Inquéritos e Questionários , Adulto JovemRESUMO
Prior studies demonstrate that most living kidney donors (LKDs) report no adverse psychosocial outcomes; however, changes in psychosocial functioning at the individual donor level have not been routinely captured. We studied psychosocial outcomes predonation and at 1, 6, 12, and 24 months postdonation in 193 LKDs and 20 healthy controls (HCs). There was minimal to no mood disturbance, body image concerns, fear of kidney failure, or life dissatisfaction, indicating no incremental changes in these outcomes over time and no significant differences between LKDs and HCs. The incidence of any new-onset adverse outcomes postdonation was as follows: mood disturbance (16%), fear of kidney failure (21%), body image concerns (13%), and life dissatisfaction (10%). Multivariable analyses demonstrated that LKDs with more mood disturbance symptoms, higher anxiety about future kidney health, low body image, and low life satisfaction prior to surgery were at highest risk of these same outcomes postdonation. It is important to note that some LKDs showed improvement in psychosocial functioning from pre- to postdonation. Findings support the balanced presentation of psychosocial risks to potential donors as well as the development of a donor registry to capture psychosocial outcomes beyond the mandatory 2-year follow-up period in the United States.
Assuntos
Afeto , Imagem Corporal , Tomada de Decisões , Medo , Transplante de Rim , Doadores Vivos/psicologia , Satisfação Pessoal , Insuficiência Renal/psicologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A new procedure was developed and applied to study immunoglobulin free light chains (FLC) in saliva of healthy subjects and patients with multiple sclerosis (MS). The procedure was based on a Western blot analysis for detection and semiquantitative evaluation of monomeric and dimeric FLCs. The FLC indices accounting for the total FLC levels and for the monomer/dimer ratios of κ and λ FLC were calculated, and the cut-off values of the FLC indices were determined to distinguish healthy state from MS disease. The obtained FLC index values were statistically different in the saliva of three groups: active MS patients, MS patients in remission and healthy subjects groups. Our FLC monomer-dimer analysis allowed differentiation between healthy state and active MS with specificity of 100% and a sensitivity of 88·5%. The developed technique may serve as a new non-invasive complementary tool to evaluate the disease state by differentiating active MS from remission with sensitivity of 89% and specificity of 80%.
Assuntos
Biomarcadores/análise , Cadeias Leves de Imunoglobulina/análise , Esclerose Múltipla/diagnóstico , Saliva/química , Adulto , Western Blotting/métodos , Feminino , Humanos , Cadeias kappa de Imunoglobulina/análise , Cadeias lambda de Imunoglobulina/análise , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
In 2012, the U.S. Food and Drug Administration issued guidelines advising kidney transplant recipients (KTRs) to discontinue mycophenolate (MPA) in preparation for pregnancy. Little is known about how this guidance has affected pregnancy and graft outcomes. The purpose of this retrospective cohort study was to investigate any association between the discontinuation of MPA and KTR pregnancy and graft outcomes. Data from the National Transplantation Pregnancy Registry included 382 cases in which KTRs managed on MPA became pregnant. Overall, 22 variables, including the time in which a KTR discontinued MPA, were assessed across four end points: miscarriages, birth defects, and 2- and 5-year postpartum graft loss. Birth defects and miscarriages were similar among KTRs who discontinued MPA >6 and <6 weeks prior to pregnancy and during the first trimester. In contrast, discontinuing MPA during the second trimester or later significantly increased the risk of miscarriages (odds ratio [OR] 9.35, 95% confidence interval [CI] 4.31-20.00, p < 0.001) and birth defects (OR 6.06, 95% CI 1.96-18.87, p = 0.002). Discontinuing MPA <6 weeks prior to pregnancy was associated with an increased risk of 5-year graft loss. For the fetus, there is value to discontinuing MPA anytime prior to the second trimester. Adhering to current guidelines does not negatively affect graft survival.
Assuntos
Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Ácido Micofenólico/uso terapêutico , Transplantados , Adulto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Humanos , Imunossupressores/uso terapêutico , Testes de Função Renal , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Despite the abundance of information on cutaneous malignancies associated with solid organ transplantation in the transplant literature, there is limited information regarding nonmalignant skin changes after transplantation. There are numerous skin toxicities secondary to immunosuppressive and other transplant-related medications that can vary in presentation, severity, and prognosis. To limit associated morbidity and mortality, solid organ transplant recipient care providers should effectively identify and manage cutaneous manifestations secondary to drug toxicity. Toxicities from the following transplant-related medications will be discussed: antithymocyte globulins, systemic steroids, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mammalian target of rapamycin inhibitors sirolimus and everolimus, basiliximab and daclizumab, belatacept, and voriconazole.
Assuntos
Imunossupressores/efeitos adversos , Transplante de Órgãos/efeitos adversos , Dermatopatias/induzido quimicamente , HumanosRESUMO
In this 12-month, multicenter, randomized, open-label, noninferiority study, de novo renal transplant recipients (RTxRs) were randomized (1:1) to receive everolimus plus low-dose tacrolimus (EVR+LTac) or mycophenolate mofetil plus standard-dose Tac (MMF+STac) with induction therapy (basiliximab or rabbit anti-thymocyte globulin). Noninferiority of composite efficacy failure rate (treated biopsy-proven acute rejection [tBPAR]/graft loss/death/loss to follow-up) in EVR+LTac versus MMF+STac was missed by 1.4%, considering the noninferiority margin of 10% (24.6% vs. 20.4%; 4.2% [-3.0, 11.4]). Incidence of tBPAR (19.1% vs. 11.2%; p < 0.05) was significantly higher, while graft loss (1.3% vs. 3.9%; p < 0.05) and composite of graft loss/death/lost to follow-up (6.1% vs. 10.5%, p = 0.05) were significantly lower in EVR+LTac versus MMF+STac groups, respectively. Mean estimated glomerular filtration rate was similar between EVR+LTac and MMF+STac groups (63.1 [22.0] vs. 63.1 [19.5] mL/min/1.73 m2 ) and safety was comparable. In conclusion, EVR+LTac missed noninferiority versus MMF+STac based on the 10% noninferiority margin. Further studies evaluating optimal immunosuppression for improved efficacy will guide appropriate dosing and target levels of EVR and LTac in RTxRs.
Assuntos
Everolimo/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Ácido Micofenólico/uso terapêutico , Tacrolimo/uso terapêutico , Adolescente , Adulto , Idoso , Estudos de Equivalência como Asunto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Humanos , Imunossupressores/uso terapêutico , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Fatores de Risco , Segurança , Adulto JovemRESUMO
In 2015, a typhoid fever outbreak began in downtown Kampala, Uganda, and spread into adjacent districts. In response, an environmental survey of drinking water source types was conducted in areas of the city with high case numbers. A total of 122 samples was collected from 12 source types and tested for Escherichia coli, free chlorine, and conductivity. An additional 37 grab samples from seven source types and 16 paired large volume (20 liter) samples from wells and springs were also collected and tested for the presence of Salmonella enterica serovar Typhi. Escherichia coli was detected in 60% of kaveras (drinking water sold in plastic bags) and 80% of refilled water bottles; free chlorine was not detected in either source type. Most jerry cans (68%) contained E. coli and had free chlorine residuals below the WHO-recommended level of 0.5 mg/liter during outbreaks. Elevated conductivity readings for kaveras, refilled water bottles, and jerry cans (compared to treated surface water supplied by the water utility) suggested that they likely contained untreated groundwater. All unprotected springs and wells and more than 60% of protected springs contained E. coli Water samples collected from the water utility were found to have acceptable free chlorine levels and no detectable E. coli While S Typhi was not detected in water samples, Salmonella spp. were detected in samples from two unprotected springs, one protected spring, and one refilled water bottle. These data provided clear evidence that unregulated vended water and groundwater represented a risk for typhoid transmission.IMPORTANCE Despite the high incidence of typhoid fever globally, relatively few outbreak investigations incorporate drinking water testing. During waterborne disease outbreaks, measurement of physical-chemical parameters, such as free chlorine residual and electrical conductivity, and of microbiological parameters, such as the presence of E. coli or the implicated etiologic agent, in drinking water samples can identify contaminated sources. This investigation indicated that unregulated vended water and groundwater sources were contaminated and were therefore a risk to consumers during the 2015 typhoid fever outbreak in Kampala. Identification of contaminated drinking water sources and sources that do not contain adequate disinfectant levels can lead to rapid targeted interventions.
Assuntos
Água Potável/microbiologia , Água Subterrânea/microbiologia , Salmonella typhi/isolamento & purificação , Febre Tifoide/microbiologia , Surtos de Doenças , Meio Ambiente , Humanos , Salmonella typhi/classificação , Salmonella typhi/genética , Febre Tifoide/epidemiologia , Uganda/epidemiologia , Poluição da Água , Abastecimento de ÁguaRESUMO
In this paper, we have reviewed the literature and report on kidney donors that are currently used at relatively low rates. Kidneys from donors with acute kidney injury (AKI) seem to have outcomes equivalent to those from donors without AKI, provided one can rule out significant cortical necrosis. Kidneys from donors with preexisting diabetes or hypertension may have marginally lower aggregate survival but still provide patients with a significant benefit over remaining on the wait list. The Kidney Donor Profile Index derives only an aggregate association with survival with a very modest C statistic; therefore, the data indicated that this index should not be the sole reason to discard a kidney, except perhaps in patients with extremely low estimated posttransplant survival scores. It is important to note that the Scientific Registry of Transplant Recipients models of risk adjustment should allay concerns regarding regulatory issues for observed outcomes falling below expectations. The successful utilization of kidneys from donation after cardiac death over the past decade shows how expanding our thinking can translate into more patients benefiting from transplantation. Given the growing number of patients on the wait list, broadening our approach to kidney acceptance could have an important impact on the population with end-stage renal disease. Many lives could be prolonged by carefully considering use of kidneys that are often discarded.
Assuntos
Seleção do Doador , Rim/fisiopatologia , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Cadáver , Humanos , Transplante de RimRESUMO
Some living kidney donors (LKDs) incur costs associated with donation, although these costs are not well characterized in the United States. We collected cost data in the 12 mo following donation from 182 LKDs participating in the multicenter prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 167, 92%) had one direct cost or more following donation, including ground transportation (86%), health care (41%), meals (53%), medications (36%), lodging (23%), and air transportation (12%). LKDs missed 33 072 total work hours, 40% of which were unpaid and led to $302 175 in lost wages (mean $1660). Caregivers lost $68 655 in wages (mean $377). Although some donors received financial assistance, 89% had a net financial loss in the 12-mo period, with one-third (33%) reporting a loss exceeding $2500. Financial burden was higher for those with greater travel distance to the transplant center (Spearman's ρ = 0.26, p < 0.001), lower household income (Spearman's ρ = -0.25, p < 0.001), and more unpaid work hours missed (Spearman's ρ = 0.52, p < 0.001). Achieving financial neutrality for LKDs must be an immediate priority for the transplant community, governmental agencies, insurance companies, nonprofit organizations, and society at large.
Assuntos
Gastos em Saúde/tendências , Falência Renal Crônica/cirurgia , Transplante de Rim/economia , Doadores Vivos , Nefrectomia/economia , Coleta de Tecidos e Órgãos/economia , Adulto , Custos e Análise de Custo , Feminino , Seguimentos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos ProspectivosRESUMO
AIM: Maternal personality traits affect child dental behaviour and have a potential link with dental treatment methods. This study aims to evaluate which maternal personality traits affect child dental behaviour. MATERIALS AND METHODS: Research was carried out upon 60 children aged between 3-12 years, who had been admitted to our clinic for tooth extraction. All children were evaluated by means of the Frankl Behavior Scale (FBS): degrees I and II represent negative behaviours, while III and IV positive behaviour. Thirty children with FBS degree III and IV were assigned to Group I and 30 children with FBS degree I and II were assigned to Group II. Children in Group I underwent tooth extraction with local anaesthesia. Children in Group II underwent tooth extraction under deep sedation. During the first visit, the mothers were tested with the Minnesota Multiphasic Personality Inventory to evaluate personality traits. All mothers in Group I and half the mothers in Group II filled a complete and valid test. RESULTS: Group I and II mothers were compared according to the test results: scores of the Minnesota Multiphasic Personality Inventory (MMPI) test were significantly higher in Group II (p<0.05). CONCLUSION: We hypotetise that character features of mothers of children with negative dental behaviour and positive dental behaviour are different and affect child dental behaviour.
Assuntos
Comportamento Infantil , Assistência Odontológica/psicologia , Mães/psicologia , Personalidade , Anestesia Dentária/métodos , Anestesia Local/métodos , Transtorno Bipolar/psicologia , Criança , Pré-Escolar , Sedação Profunda/métodos , Depressão/psicologia , Feminino , Humanos , Hipocondríase/psicologia , Histeria/psicologia , Introversão Psicológica , Masculino , Relações Mãe-Filho , Negativismo , Inventário de Personalidade , Transtornos Psicóticos/psicologia , Extração Dentária/métodosRESUMO
Autism spectrum disorders are severe neurodevelopmental disorders, marked by impairments in reciprocal social interaction, delays in early language and communication, and the presence of restrictive, repetitive and stereotyped behaviors. Accumulating evidence suggests that dysfunction of the amygdala may be partially responsible for the impairment of social behavior that is a hallmark feature of ASD. Our studies suggest that a valproic acid (VPA) rat model of ASD exhibits an enlargement of the amygdala as compared to controls rats, similar to that observed in adolescent ASD individuals. Since recent research suggests that altered neuronal development and morphology, as seen in ASD, may result from a common post-transcriptional process that is under tight regulation by microRNAs (miRs), we examined genome-wide transcriptomics expression in the amygdala of rats prenatally exposed to VPA, and detected elevated miR-181c and miR-30d expression levels as well as dysregulated expression of their cognate mRNA targets encoding proteins involved in neuronal system development. Furthermore, selective suppression of miR-181c function attenuates neurite outgrowth and branching, and results in reduced synaptic density in primary amygdalar neurons in vitro. Collectively, these results implicate the small non-coding miR-181c in neuronal morphology, and provide a framework of understanding how dysregulation of a neurodevelopmentally relevant miR in the amygdala may contribute to the pathophysiology of ASD.
Assuntos
Tonsila do Cerebelo/metabolismo , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , MicroRNAs/metabolismo , Tonsila do Cerebelo/patologia , Animais , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/patologia , Modelos Animais de Doenças , Neurônios/metabolismo , Neurônios/patologia , Ratos , Comportamento Social , Transcriptoma , Ácido ValproicoRESUMO
The new national Kidney Allocation System of the Organ Procurement and Transplantation Network (OPTN), effective as of December 4, 2014, was designed to improve the chances of transplanting the most highly sensitized patients on the waitlist, those with calculated panel reactive antibody values of 98%, 99% and 100%. Recently, it was suggested that these highly sensitized patients will experience inequitable access, given the reported high prevalence of antibodies to HLA-DP, and the fact that only about 1/3 of deceased donors are typed for HLA-DP antigens. Here we report that 320/2948 flow cytometric crossmatches performed for the Northwestern transplant program over the past 28 months were positive solely due to HLA-DP donor-specific antibodies (11%; 16.5% of patients with HLA antibodies-sensitized patients). We further show that 58/207 (12%) HLA-DR serologically matched donor-recipient pairs had a positive B cell flow crossmatch due to donor-specific HLA class II antibodies, and 2/34 (6%) serologic zero-HLA-A-B-DR mismatch had a positive flow crossmatch due to HLA-DSA. We therefore provide information regarding the necessity and importance of complete donor HLA typing including both chains of the HLA-DP antigen (encoded by HLA-DPA1 and HLA-DPB1) at the time of organ offer.
Assuntos
Cadeias alfa de HLA-DP/imunologia , Cadeias beta de HLA-DP/imunologia , Hipersensibilidade/imunologia , Transplante de Órgãos , Alocação de Recursos/legislação & jurisprudência , Alocação de Recursos/normas , Obtenção de Tecidos e Órgãos/organização & administração , Citometria de Fluxo , Histocompatibilidade/imunologia , Teste de Histocompatibilidade , Humanos , Isoanticorpos/imunologia , Doadores de Tecidos , Estados UnidosRESUMO
Limited information exists on the predonation costs incurred by eventual living kidney donors (LKDs). Expenses related to completion of the donation evaluation were collected from 194 LKDs participating in the multi-center, prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 187, 96%) reported one or more direct costs, including ground transportation (80%), healthcare (24%), lodging (17%) and air transportation (14%), totaling $101 484 (USD; mean = $523 ± 942). Excluding paid vacation or sick leave, donor and companion lost wages totaled $35 918 (mean = $187 ± 556) and $14 378 (mean = $76 ± 311), respectively. One-third of LKDs used paid vacation or sick leave to avoid incurring lost wages. Few LKDs reported receiving financial support from the transplant candidate (6%), transplant candidate's family (3%), a nonprofit organization (3%), the National Living Donor Assistance Center (7%), or transplant center (3%). Higher total costs were significantly associated with longer distance traveled to the transplant center (p < 0.001); however, total costs were not associated with age, sex, race/ethnicity, household income, marital status, insurance status, or transplant center. Moderate predonation direct and indirect costs are common for adults who complete the donation evaluation. Potential LKDs should be advised of these possible costs, and the transplant community should examine additional strategies to reimburse donors for them.
Assuntos
Custos e Análise de Custo , Gastos em Saúde/tendências , Falência Renal Crônica/cirurgia , Transplante de Rim/economia , Doadores Vivos , Nefrectomia/economia , Obtenção de Tecidos e Órgãos/economia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
PURPOSE OF REVIEW: There are several monoclonal and polyclonal antibodies used in renal transplantation today, this article will discuss several agents, their updates and newer agents. RECENT FINDINGS: Antithymocyte globulin and interleukin-2 (IL-2) receptor blocker continue to be used as induction agents. The risk of acute rejection was higher in IL-2 receptor blockers mainly in the first year, but graft survivals were similar in both groups long term. Belatacept is the only approved intravenous maintenance immunosuppressive therapy which provides the benefit of glomerular filtration rate preservation, but it was associated with a higher risk of acute rejection and post-transplant lymphoproliferative disorder. Bortezomib may help decrease donor-specific antibody levels, but there are limited data to support its use for desensitization or rejection. Eculizumab may help in antibody-mediated rejection in some cases but has not shown promising long-term effects in high-risk individuals. Newer agents have been continuously tested for improved efficacy and safety. SUMMARY: Transplantation is the standard of care for end-stage renal disease patients, but we still have a long way to go, as we need to improve long-term outcomes. The manipulation of the immune system is a delicate undertaking, with risks of adverse events; therefore, risk versus benefit needs to be carefully evaluated and treatment needs to be individualized.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Imunossupressores/uso terapêutico , Falência Renal Crônica/terapia , Transplante de Rim , Anticorpos Monoclonais/imunologia , Humanos , Falência Renal Crônica/imunologiaRESUMO
This editorial offers a counterpoint to the findings of increased mortality in living kidney donors in a study by Mjøen et al that has been widely discussed in the transplant community.
Assuntos
Transplante de Rim/efeitos adversos , Doadores Vivos , Coleta de Tecidos e Órgãos/efeitos adversos , Feminino , Humanos , MasculinoRESUMO
AIMS: To determine whether antivirus and/or islet cell antibodies can be detected in healthy pregnant mothers without diabetes and/or their offspring at birth in two winter viral seasons. METHODS: Maternal and cord blood sera from 107 healthy pregnant women were tested for islet cell autoantibodies using radioligand binding assays and for anti-rotavirus and anti-CoxB3 antibody using an enzyme-linked immunosorbent assay. RESULTS: Glutamic acid decarboxylase (GAD)65 autoantibodies and rotavirus antibodies, present in both maternal and cord blood sera, correlated with an odds ratio of 6.89 (95% CI: 1.01-46.78). For five, 22 and 17 pregnancies, antibodies to GAD65, rotavirus and CoxB3, respectively, were detected in cord blood only and not in the corresponding maternal serum. In 10 pregnancies, rotavirus antibody titres in the cord blood exceeded those in the corresponding maternal serum by 2.5-5-fold. Increased antibody titres after the 20(th) week of gestation suggested CoxB3 infection in one of the 20 pregnancies and rotavirus in another. CONCLUSION: The concurrent presence of GAD65 antibodies in cord blood and their mothers may indicate autoimmune damage to islet cells during gestation, possibly caused by cross-placental transmission of viral infections and/or antivirus antibodies. Cord blood antibody titres that exceed those of the corresponding maternal sample by >2.5-fold, or antibody-positive cord blood samples with antibody-negative maternal samples, may imply an active in utero immune response by the fetus.