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2.
Medicine (Baltimore) ; 99(10): e19301, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150064

RESUMO

We treated skin sclerosis with triple therapy consisting of a glucocorticoid, intravenous cyclophosphamide, and double-filtration plasmapheresis. The objective of this study was to analyze its effectiveness in a case series of patients who received triple therapy.We enrolled 8 patients with diffuse cutaneous systemic sclerosis (dcSSc) who received triple therapy at our hospital from 2008 to 2016. We analyzed the mean change in the modified Rodnan skin score (mRSS), percentage of the predicted forced vital capacity (%FVC), percentage of the predicted carbon monoxide diffusing capacity (%DLCO), and serum KL-6 levels from baseline to follow-up.All patients were treated with an intermediate dose of oral prednisolone (30.6 ±â€Š2.1 mg/day) initially. The mean cumulative dose of intravenous cyclophosphamide was 1.4 ±â€Š0.2 g. The mean mRSS decreased significantly at follow-up compared with that at baseline (27.0 ±â€Š3.3 vs 15.8 ±â€Š3.5; P = .03). At the end of the treatment, the mean %FVC and %DLCO were improved moderately, although the differences were not significant. The serum KL-6 levels decreased from 578.9 ±â€Š146.5 to 205.3 ±â€Š43.1 U/ml (P = .02). No significant correlation was found between the change in mRSS or disease duration and the initial skin score severity.Triple therapy may improve skin sclerosis, with effectiveness equal or superior to other reported treatments. This preliminary case series demonstrates the potential of triple therapy for treating dcSSc. However, prospective studies with long-term follow-up should be performed to assess its role.


Assuntos
Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Plasmaferese , Prednisolona/uso terapêutico , Esclerodermia Difusa/terapia , Administração Oral , Idoso , Terapia Combinada , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Mucina-1/sangue , Capacidade de Difusão Pulmonar , Estudos Retrospectivos , Esclerodermia Difusa/tratamento farmacológico , Esclerodermia Difusa/fisiopatologia , Resultado do Tratamento , Capacidade Vital
3.
BMJ ; 368: m421, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188597

RESUMO

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a small to medium vessel vasculitis associated with excess morbidity and mortality. This review explores how management of AAV has evolved over the past two decades with pivotal randomized controlled trials shaping the management of induction and maintenance of remission. Contemporary AAV care is characterized by approaches that minimize the cumulative exposure to cyclophosphamide and glucocorticoids, increasingly use rituximab for remission induction and maintenance, and consider therapies with less toxicity (for example, methotrexate, mycophenolate mofetil) for manifestations of AAV that do not threaten organ function or survival. Simultaneously, improvements in outcomes, such as renal and overall survival, have been observed. Additional trials and observational studies evaluating the comparative effectiveness of agents for AAV in various patient subgroups are needed. Prospective studies are necessary to assess the effect of psychosocial interventions on patient reported outcomes in AAV. Despite the expanding array of treatments for AAV, little guidance on how to personalize AAV care is available to physicians.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Imunossupressores/uso terapêutico , Azatioprina , Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Indução de Remissão , Rituximab/uso terapêutico
4.
N Engl J Med ; 382(12): 1093-1102, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32187469

RESUMO

BACKGROUND: The treatment of chronic sciatica caused by herniation of a lumbar disk has not been well studied in comparison with acute disk herniation. Data are needed on whether diskectomy or a conservative approach is better for sciatica that has persisted for several months. METHODS: In a single-center trial, we randomly assigned patients with sciatica that had lasted for 4 to 12 months and lumbar disk herniation at the L4-L5 or L5-S1 level in a 1:1 ratio to undergo microdiskectomy or to receive 6 months of standardized nonoperative care followed by surgery if needed. Surgery was performed by spine surgeons who used conventional microdiskectomy techniques. The primary outcome was the intensity of leg pain on a visual analogue scale (ranging from 0 to 10, with higher scores indicating more severe pain) at 6 months after enrollment. Secondary outcomes were the score on the Oswestry Disability Index, back and leg pain, and quality-of-life scores at 6 weeks, 3 months, 6 months, and 1 year. RESULTS: From 2010 through 2016, a total of 790 patients were screened; of those patients, 128 were enrolled, with 64 in each group. Among the patients assigned to undergo surgery, the median time from randomization to surgery was 3.1 weeks; of the 64 patients in the nonsurgical group, 22 (34%) crossed over to undergo surgery at a median of 11 months after enrollment. At baseline, the mean score for leg-pain intensity was 7.7 in the surgical group and 8.0 in the nonsurgical group. The primary outcome of the leg-pain intensity score at 6 months was 2.8 in the surgical group and 5.2 in the nonsurgical group (adjusted mean difference, 2.4; 95% confidence interval, 1.4 to 3.4; P<0.001). Secondary outcomes including the score on the Owestry Disability Index and pain at 12 months were in the same direction as the primary outcome. Nine patients had adverse events associated with surgery, and one patient underwent repeat surgery for recurrent disk herniation. CONCLUSIONS: In this single-center trial involving patients with sciatica lasting more than 4 months and caused by lumbar disk herniation, microdiskectomy was superior to nonsurgical care with respect to pain intensity at 6 months of follow-up. (Funded by Physicians' Services Incorporated Foundation; ClinicalTrials.gov number, NCT01335646.).


Assuntos
Tratamento Conservador , Discotomia , Glucocorticoides/administração & dosagem , Deslocamento do Disco Intervertebral/cirurgia , Modalidades de Fisioterapia , Ciática/terapia , Adulto , Tratamento Conservador/métodos , Estudos Cross-Over , Discotomia/efeitos adversos , Feminino , Seguimentos , Humanos , Injeções Epidurais , Análise de Intenção de Tratamento , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/tratamento farmacológico , Masculino , Dor/etiologia , Medição da Dor , Satisfação do Paciente , Complicações Pós-Operatórias , Qualidade de Vida , Ciática/etiologia , Ciática/cirurgia , Resultado do Tratamento
5.
Rev. clín. esp. (Ed. impr.) ; 220(2): 86-93, mar. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-186417

RESUMO

Introducción: Aunque las guías de práctica clínica recomiendan un ajuste continuado del tratamiento del asma, reduciendo la medicación de mantenimiento cuando se alcanza el control (step-down), existen pocos estudios de práctica clínica habitual orientados a recabar información de los factores que condicionan su fracaso. Objetivo: Determinar los factores que condicionan en la práctica clínica habitual el fracaso del step-down en los pacientes asmáticos moderados-graves controlados con una combinación de glucocorticoides inhalados/agonistas beta-2 adrenérgicos de acción larga. Método: Estudio multicéntrico retrospectivo sobre 374 pacientes con asma moderada-grave controlada con glucocorticoides inhalados/agonistas beta-2 adrenérgicos de acción larga en quienes el facultativo indicó en 2016 un step-down. Resultados: El step-down fracasó en el 41,7%. Los factores relacionados con el fracaso fueron: la mayor edad del paciente (p=0,006), la presencia de 2 o más comorbilidades (p=0,016), el mayor nivel de gravedad (persistente grave vs. persistente moderada) (p<0,001), la mayor edad al diagnóstico (>40 años) (p=0,045), cuanto más alto es el escalón terapéutico previo (p=0,003) y posterior al cambio (p<0,001), cuanto menor sea el tiempo de mejoría/control previo al cambio (p=0,019), el FEV1 más bajo (p=0,001) y un peor Asthma Control Test o Asthma Control Questionnaire antes del step-down (p<0,001). El análisis de regresión logística mostró que existe una mayor probabilidad (odds ratio [IC 95%] de fracaso del step-down en los pacientes más añosos: OR 0,983 [0,969-0,997], con asma grave vs. moderada: OR 0,537 [0,292-0,985] y mayor probabilidad de éxito si llevan más de 6 meses con la enfermedad controlada: OR 2,253 [1,235-4,112]). Conclusión: En condiciones de práctica clínica habitual el step-down fracasa en un porcentaje alto de pacientes y se recomienda indicarlo cuando el paciente lleve más de 6 meses controlado


Background: Although the clinical practice guidelines recommend continuous adjustment of asthma treatment and reducing the maintenance drugs when achieving control (step-down), there are few studies of standard clinical practice aimed at collecting information on the factors that determine step-down failure. Objective: To determine the factors that determine step-down failure in standard clinical practice of patients with moderate-severe asthma controlled by a combination of inhaled glucocorticoids and long-acting beta agonists. Methods: A multicentre retrospective study included 374 patients with moderate-severe asthma controlled with inhaled glucocorticoids and long-acting beta agonists for whom the physician indicated a step-down in 2016. Results: The step-down failed in 41.7% of the patients. The following factors were related to failure: greater patient age (P=.006), presence of at least 2 comorbidities (P=.016), greater severity level (severe persistent vs. moderate persistent) (P<.001), greater age at diagnosis (>40 years) (P=.045), the higher the therapeutic step before (P=.003) and after the change (P<.001), the shorter the time of improvement/control prior to the change (P=.019), lower FEV1 (P=.001) and a poorer Asthma Control Test score or Asthma Control Questionnaire score before the step-down (P<.001). The logistic regression analysis showed a higher probability of step-down failure in the more elderly patients (OR, 0.983; 95% CI 0.969-0.997) and those with severe asthma compared to those with moderate asthma (OR, 0.537; 95% CI 0.292-0.985), as well as an increased probability of success if the patients had the disease controlled for more than 6 months (OR, 2.253; 95% CI 1.235-4.112). Conclusion: In standard clinical practice conditions, step-down fails in a high percentage of patients, and the suggestion is to indicate step-down when the patient has had more than 6 months of disease control


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Glucocorticoides/uso terapêutico , Asma/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Asma/prevenção & controle , Exacerbação dos Sintomas , Comorbidade , Rinite Alérgica/epidemiologia , Pólipos Nasais/epidemiologia , Antagonistas de Leucotrienos/uso terapêutico
6.
Rev. clín. esp. (Ed. impr.) ; 220(2): 109-114, mar. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-186420

RESUMO

Introducción: El síndrome hemofagocítico (SHF) es un trastorno inmunológico grave caracterizado por una inflamación descontrolada con fracaso multiorgánico. Puede estar desencadenado por infecciones víricas, bacterianas, fúngicas o parasitarias. Se describe nuestra experiencia de SHF asociado a infecciones y se estima su incidencia local. Material y método: Estudio retrospectivo observacional de SHF asociado a infecciones en adultos atendidos en el Servicio de Patología Infecciosa de un hospital universitario durante 5años y revisión de las series publicadas en Europa. Resultados: En 2 mujeres con enfermedad de Crohn, el SHF se asoció a infección por citomegalovirus y a leishmaniosis visceral (mieloma múltiple 1, tumor sólido 2, sin enfermedad evidente 1) en 4 pacientes (3 hombres). Fallecieron 2 enfermos. La incidencia estimada fue 0,58/100.000/año. Las series publicadas son heterogéneas. Conclusiones: El SHF asociado a infecciones debe de ser más frecuente de lo descrito. El entorno geográfico puede influir en las infecciones desencadenantes (en nuestro medio, debe buscarse Leishmania)


Background: Haemophagocytic syndrome (HPS) is a severe immunological disorder characterised by uncontrolled inflammation and multiple organ failure. HPS can be triggered by viral, bacterial, fungal and parasitical infections. We report our experience with infection-related HPS and estimate its local incidence. Material and method: We conducted an observational retrospective study of infection-associated HPS in patients treated in the Department of Infectious Diseases of a university hospital within a 5-year period, as well as a review of the published series in Europe. Results: HPS was associated with infection by cytomegalovirus in 2 women with Crohn's disease and was associated with visceral leishmaniosis in 4 patients (3 men, 1 woman; 1 case of multiple myeloma; 2 cases of solid tumours; 1 case of no apparent disease). Two patients died, and the estimated incidence rate was 0.58/100,000 inhabitants/year. The published series are mixed. Conclusions: Infection-related HPS must be more common than reported. The geographical environment can influence the triggering infections (in our environment, Leishmania should be considered)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Idoso , Linfo-Histiocitose Hemofagocítica/diagnóstico , Insuficiência de Múltiplos Órgãos/diagnóstico , Etoposídeo/uso terapêutico , Glucocorticoides/uso terapêutico , Estudos Retrospectivos , Infecções por Citomegalovirus/diagnóstico , Leishmaniose/diagnóstico , Mieloma Múltiplo/complicações , Doença de Crohn/complicações , Resultado do Tratamento
8.
Medicine (Baltimore) ; 99(8): e19227, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080120

RESUMO

Lateral epicondylitis (LE) is a common musculoskeletal disorder for which an effective treatment strategy remains unknown. The goal of this study is to examine whether acupuncture is more effective than injection of glucocorticoid in adults with LE.Adults with LE received either acupuncture or injection of glucocorticoid were followed-up for 6 months. All patients assessed before treatment, 0, 3 months, and 6 months after the therapy. Outcome measures consisted of visual analog scores (VAS) and the Mayo elbow performance score (MEPS).The acupuncture group and the corticosteroid group did not differ on demographic or clinical characteristics (P < .05). VAS and MEPS score was not significantly different between 2 groups at 0 and 3 months. MEPS scores were significantly lower in the corticosteroid group at 6 months, compared with those in the acupuncture group (P < .05). However, the VAS score was not significantly different (P > .05). There were no complications related to the use of acupuncture or corticosteroid injection.We found that both methods were effective for external humeral epicondylitis. However, after 6 months of treatment, patients with chronic LE with acupuncture achieved pain relief and function improve significantly, exceeding the effect of corticosteroid injection.


Assuntos
Terapia por Acupuntura/métodos , Anti-Inflamatórios/uso terapêutico , Glucocorticoides/uso terapêutico , Cotovelo de Tenista/terapia , Idoso , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Amplitude de Movimento Articular , Estudos Retrospectivos , Cotovelo de Tenista/tratamento farmacológico
9.
Eur J Endocrinol ; 182(4): C13-C15, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32061161

RESUMO

Endocrine disorders such as Cushing's syndrome and hypothyroidism may cause weight gain and exacerbate metabolic dysfunction in obesity. Other forms of endocrine dysfunction, particularly gonadal dysfunction (predominantly testosterone deficiency in men and polycystic ovarian syndrome in women), and abnormalities of the hypothalamic-pituitary-adrenal axis, the growth hormone-IGF-1 system and vitamin D deficiency are common in obesity. As a result, endocrinologists may be referred people with obesity for endocrine testing and asked to consider treatment with various hormones. A recent systematic review and associated guidance from the European Society of Endocrinology provide a useful evidence summary and clear guidelines on endocrine testing and treatment in people with obesity. With the exception of screening for hypothyroidism, most endocrine testing is not recommended in the absence of clinical features of endocrine syndromes in obesity, and likewise hormone treatment is rarely needed. These guidelines should help reduce unnecessary endocrine testing in those referred for assessment of obesity and encourage clinicians to support patients with their attempts at weight loss, which if successful has a good chance of correcting any endocrine dysfunction.


Assuntos
Doenças do Sistema Endócrino/complicações , Doenças do Sistema Endócrino/diagnóstico , Obesidade/etiologia , Síndrome de Cushing/complicações , Feminino , Glucocorticoides/metabolismo , Hormônios/análise , Hormônios/uso terapêutico , Humanos , Hipogonadismo/complicações , Hipotireoidismo/complicações , Masculino , Síndrome do Ovário Policístico/complicações
10.
Artigo em Inglês | MEDLINE | ID: mdl-32109749

RESUMO

Obtaining longitudinal endocrinological data from free-ranging animals remains challenging. Steroid hormones can be extracted sequentially from non-invasively sampled biologically inert keratinous tissues, such as feathers, nails, hair and whiskers. However, uncertainty regarding the type and levels of steroids incorporated into such tissues complicates their utility in wildlife studies. Here, we developed a novel, comprehensive method to analyze fourteen C19 and fourteen C21 steroids deposited chronologically along the length of seal whiskers in a single, 6-minute chromatographic step, using ultra-performance convergence chromatography-tandem mass spectrometry. The limits of detection and quantification ranged from 0.01 to 2 ng/mL and from 0.1 to 10 ng/mL, respectively. The accuracy and precision were within acceptable limits for steroids at concentrations ≥2 ng/mL. The recovery (mean = 107.5% at 200 ng/mL), matrix effect and process efficiency of steroids evaluated, using blanked whisker matrix samples, were acceptable. The method was applied to the analysis of steroid hormone levels in adult female whisker segments obtained from southern elephant seals (Mirounga leonina), n = 10, and two fur seal species, Antarctic fur seals (Arctocephalus gazella; n = 5) and subantarctic fur seals (Arctocephalus tropicalis; n = 5), sampled between 2012 and 2017. In the whisker subsamples analyzed (n = 71), the median concentration of steroid hormones detected above the LOQ ranged from 2.0 to 273.7 pg/mg. This was the first extraction of multiple C19 and C21 steroids, including their C11-oxy metabolites, from the whiskers of mammals. Measuring hormones sequentially along the whisker lengths can contribute to our understanding of the impact of stress associated with environmental/climate changes that affect the health, survival of organisms, as well as to delineate the reproductive cycles of free-living mammals with cryptic life stages.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Esteroides/análise , Espectrometria de Massas em Tandem/métodos , Vibrissas/química , Androgênios/análise , Animais , Feminino , Otárias , Glucocorticoides/análise , Ensaios de Triagem em Larga Escala , Limite de Detecção , Modelos Lineares , Progestinas/análise , Reprodutibilidade dos Testes
11.
N Engl J Med ; 382(7): 622-631, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053298

RESUMO

BACKGROUND: More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD). RESULTS: Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.).


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Glucocorticoides/administração & dosagem , Falência Renal Crônica/prevenção & controle , Troca Plasmática , Administração Oral , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Terapia Combinada , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/uso terapêutico , Incidência , Quimioterapia de Indução , Nefropatias/complicações , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Troca Plasmática/efeitos adversos , Rituximab/uso terapêutico
12.
Medicine (Baltimore) ; 99(7): e19266, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049868

RESUMO

Despite many clinical trials on cervical epidural steroid injections, the indications for and long-standing outcomes of this treatment remain controversial. We evaluated the outcomes and indications for transforaminal cervical epidural steroid injection (TCESI) in patients with moderate to severe disability.We prospectively gathered data from patients with 1 or 2-level cervical degenerative disease (herniated disc, foraminal stenosis) with moderate to severe disability (3.5 < initial visual analog scale < 6.5, 15 < Neck Disability Index < 35) and greater than 12 weeks of pain, despite conservative treatment. Patients with persistent disability and those who desired surgical intervention underwent decompression surgery. The clinical and demographic characteristics were compared between groups.Of the 309 patients who underwent TCESI, 221 (72%) did not receive surgical treatment during the 1-year follow-up period. The remaining 88 patients (28%) underwent surgery at a mean of 4.1 months after initial TCESI. Patients who underwent injection alone showed a significant decrease in disability and pain that persisted until the 1-year follow-up visit (P < .05). In patients who underwent surgery, the mean disability and pain scores after injection did not decrease for several months, although the scores significantly decreased up to 1 year after surgery (P < .05).The TCESI significantly decreased pain and disability in the moderate to severe disability group up to 1 year after injection. We recommend cervical TCESI as an initial treatment with moderate to severe disability patients.


Assuntos
Vértebras Cervicais , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Degeneração do Disco Intervertebral/tratamento farmacológico , Feminino , Humanos , Injeções Epidurais , Degeneração do Disco Intervertebral/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
13.
Medicine (Baltimore) ; 99(5): e18857, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000387

RESUMO

RATIONALE: IgG4-related disease (IgG4-RD) is a slowly progressing inflammatory disease that can involve multiple organ systems. There is considerable overlap between IgG4-RDs and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Herein, we present an unusual case of IgG4-associated tubulointerstitial nephritis (IgG4-TIN) and ANCA-associated glomerulonephritis (ANCA-GN) co-occurring with C3 glomerulonephritis (C3GN). PATIENT CONCERNS: A 72-year-old male was admitted to hospital because of fever and fatigue. He was diagnosed with elevated serum creatinine and IgG4 levels, and was positive for ANCA. DIAGNOSIS: Initially, the pathology supported a diagnosis of IgG4-TIN and ANCA-GN; however, further examination revealed he also had C3GN. INTERVENTIONS: The patient was treated with methylprednisolone and cyclophosphamide and received regular follow-up care. OUTCOMES: After treatment, the patient no longer exhibited fever or fatigue and had no complications. The seven-month follow-up showed downward trends in IgG4 and MPO-ANCA levels and stable 24-hour urine protein, serum creatinine levels. LESSONS: Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis and IgG4-associated tubulointerstitial nephritis with C3glomerulonephritis rarely occur simultaneously. Laboratory analysis and pathology are both needed to ensure diagnostic accuracy. However, in this case, the three diseases overlapped to such a large extent that achieving a definitive diagnosis was particularly challenging. Timely and accurate diagnosis is crucial for selecting the best treatment course and optimizing patient outcome.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Glomerulonefrite/diagnóstico , Nefrite Intersticial/diagnóstico , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Complemento C3/imunologia , Ciclofosfamida/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/imunologia , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina G/imunologia , Imunossupressores/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/imunologia
14.
Medicine (Baltimore) ; 99(5): e19026, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000449

RESUMO

INTRODUCTION: Entropion and secondary trichiasis can lead to irritative symptoms and essential damage of ocular surface. There is no literature reporting the lower eyelid entropion related to thyroid-associated ophthalmopathy (TAO), let alone the treatment. Treatment based on etiology may yield effective and sustained results. We report 3 case reports of lower eyelid entropion associated with TAO, and provide an effective and persistent alternative to cure this entropion via the administration of shallow periorbital injections of triamcinolone acetonide (TA). PATIENT CONCERNS: Three patients presented irritative symptoms of ocular surface and diplopia. DIAGNOSIS: According to thyroid dysfunction, physical examination, and imaging findings of extraocular muscle involvement, TAO and unilateral or bilateral lower eyelid entropion were diagnosed. INTERVENTIONS: We administered shallow periorbital injections of TA to the affected eye at 3- to 4-week intervals depending on clinical response. OUTCOMES: All patients underwent complete correction of the lower eyelid entropion and no recurrence was found. CONCLUSION: The cause of lower eyelid entropion related to TAO might be the immunoinflammatory reaction of the lower eyelid retractors, enhancing the traction of pulling the lower eyelid inferoposteriorly. This condition can be treated with shallow periorbital injections of TA. Histopathological evidence and randomized controlled trials are expected to confirm our hypothesis.


Assuntos
Entrópio/tratamento farmacológico , Entrópio/etiologia , Glucocorticoides/administração & dosagem , Oftalmopatia de Graves/complicações , Triancinolona Acetonida/administração & dosagem , Adulto , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade
15.
Medicine (Baltimore) ; 99(5): e19036, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000451

RESUMO

RATIONALE: Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell proliferative disorder that consistently precedes multiple myeloma. Peripheral neuropathy in patients with IgG-MGUS tends to vary in clinical phenotype. We report a rare case of a patient with IgG-MGUS who had nonsystemic vasculitic neuropathy (NSVN). PATIENT CONCERNS: A 56-year-old Japanese woman presented with progressive sensory ataxia with episodic paresthesia. Her clinical and laboratory values were compatible with IgG-MGUS. A nerve conduction study suggested possible chronic inflammatory demyelinating polyneuropathy. However, intravenous immunoglobulin therapy was not effective. A sural nerve biopsy specimen revealed mildly reduced myelinated fiber density and myelin ovoid formation, with epineural arterioles infiltrated by inflammatory cells. DIAGNOSES: We accordingly diagnosed her condition as NSVN. INTERVENTIONS: She was accordingly started on oral prednisolone (40 mg/d) at 3 months after the onset of her neurological symptoms. OUTCOMES: At 1 year after the oral prednisolone treatment was begun, the patient's neurological symptoms showed no worsening. LESSONS: These findings indicate NSVN as a possible cause of peripheral neuropathy in patients with IgG-MGUS. Cumulatively, our findings highlight the need for a nerve biopsy for peripheral neuropathy in patients with IgG-MGUS as a possible cause of NSVN. The early diagnosis of NSVN is expected to be beneficial for such patients.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Doenças do Sistema Nervoso Periférico/diagnóstico , Vasculite/diagnóstico , Idoso , Biópsia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina G , Gamopatia Monoclonal de Significância Indeterminada/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Prednisolona/uso terapêutico , Vasculite/tratamento farmacológico
16.
Medicine (Baltimore) ; 99(3): e18759, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011461

RESUMO

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially lethal disorder, characterized by a dysregulation of the immune response, leading to a severe inflammatory syndrome. Epstein-Barr virus (EBV)-associated HLH is a form of secondary HLH, a fulminant presentation of an otherwise benign viral infection. PATIENT CONCERNS: We report the case of a 3-year-old girl who presented with fever, signs of accute upper respiratory tract infection and spontaneous, disseminated ecchymoses. Initial laboratory tests revealed pancytopenia. A bone marrow aspirate was performed, which revealed megaloblasts and numerous macrophages, with abundant foamy cytoplasm. Megaloblastic anemia was excluded, as the levels of vitamin B12 and folic acid were both within normal ranges. DIAGNOSIS: Hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, and splenomegaly were relevant criteria for the diagnosis of HLH, in accordance with the bone marrow specimen. Positive immunoglobulin M antibodies for EBV were supportive of an acute EBV infection, which was the most probable trigger of HLH. The patient's evolution was complicated by a massive epistaxis, in the context of thrombocytopenia which required plasma, thrombocyte, and erythrocyte substitutes. INTERVENTION: The patient was started on a treatment regimen of 8 weeks with etoposide and dexamethasone. OUTCOME: Her evolution was favorable, the treatment being successful in remission induction. CONCLUSION: Our case emphasizes the diagnostic challenges of HLH, in a patient with EBV infection whose evolution was hindered by a severe epistaxis, with potentially fatal outcome.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Linfo-Histiocitose Hemofagocítica/virologia , Antibioticoprofilaxia , Transfusão de Componentes Sanguíneos , Pré-Escolar , Terapia Combinada , Dexametasona/uso terapêutico , Diagnóstico Diferencial , Etoposídeo/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Linfo-Histiocitose Hemofagocítica/terapia
18.
Eur J Endocrinol ; 182(4): 447-457, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32069218

RESUMO

Context: Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes. Objective: Test the effects of a diet intervention with added exercise on glucocorticoid metabolism. Design: Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX). Setting: Umeå University Hospital. Participants: Men and women with type 2 diabetes treated with lifestyle modification ± metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism. Main outcome measures: Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD11B1 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy. Results: Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5α-THF + 5ß-THF/THE in urine increased in both groups. Conclusions: These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Dieta Redutora/métodos , Exercício/fisiologia , Glucocorticoides/metabolismo , Perda de Peso/fisiologia , Adulto , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Dieta Paleolítica , Terapia por Exercício/métodos , Feminino , Técnica Clamp de Glucose , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Resistência à Insulina , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento
19.
BMC Ecol ; 20(1): 12, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070331

RESUMO

BACKGROUND: Glucocorticoids mediate responses to perceived stressors, thereby restoring homeostasis. However, prolonged glucocorticoid elevation may cause homeostatic overload. Using extensive field investigations of banded mongoose (Mungos mungo) groups in northern Botswana, we assessed the influence of reproduction, predation risk, and food limitation on apparent homeostatic overload (n=13 groups, 1542 samples from 268 animals). We experimentally manipulated reproduction and regulated food supply in captive mongooses, and compared their glucocorticoid responses to those obtained from free-living groups. RESULTS: At the population level, variation in glucocorticoid levels in free-living mongooses was explained by food limitation: fecal organic matter, recent rainfall, and access to concentrated anthropogenic food resources. Soil macrofauna density and reproductive events explained less and predation risk very little variation in glucocorticoid levels. Reproduction and its associated challenges alone (under regulated feeding conditions) increased glucocorticoid levels 19-fold in a captive group. Among free-living groups, glucocorticoid elevation was seasonal (occurring in late dry season or early wet season when natural food resources were less available), but the timing of peak glucocorticoid production was moderated by access to anthropogenic resources (groups with fewer anthropogenic food sources had peaks earlier in dry seasons). Peak months represented 12- and 16-fold increases in glucocorticoids relative to nadir months with some animals exhibiting 100-fold increases. Relative to the captive group nadir, some free-living groups exhibited 60-fold increases in peak glucocorticoid levels with some animals exhibiting up to 800-fold increases. Most of these animals exhibited 1- to 10-fold increases relative to the captive animal peak. CONCLUSIONS: Banded mongooses exhibit seasonal chronic glucocorticoid elevation, associated primarily with food limitation and secondarily with reproduction. Magnitude and duration of this elevation suggests that this may be maladaptive for some animals, with possible fitness consequences. In late dry season, this population may face a convergence of stressors (food limitation, agonistic encounters at concentrated food resources, evictions, estrus, mate competition, parturition, and predation pressure on pups), which may induce homeostatic overload.


Assuntos
Herpestidae , Animais , Fezes , Feminino , Glucocorticoides , Reprodução , Estações do Ano
20.
Water Res ; 174: 115561, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32087415

RESUMO

Glucocorticoids (GCs) are one of the most prescribed pharmaceutical classes worldwide. They have reached the focus as environmental pollutants in the current scientific research, due to their potential risks to aquatic organisms even in the lower ng L-1 range. The objective of this study was to determine the kinetic behavior of selected GCs and to identify their main transformation products (TPs) in lab scaled biodegradation experiments. Therefore, we analyzed the removal of 13 GCs in aerated incubation experiments with activated sludge taken from a German municipal wastewater treatment plant (WWTP) as inoculum. For all steroids, an exponential decrease of the concentrations was observed, which was modelled by pseudo-first order kinetics. Overall, the rate constants kbiol. ranged from 0.07 L gss-1 d-1 (triamcinolone acetonide) to 250 L gss-1 d-1 (prednisolone). These results emphasize the broad variation in the biodegradability and recalcitrance of certain GCs. The selection of the studied GCs enabled a deduction of microbiological stability related to functional groups. Based on the identified TPs, a variety of enzymatically mediated reactions were postulated. Moreover, the identified TPs are characterized by an intact steroid core structure. Thus residual endocrine activity cannot be ruled out. The main observed reactions were regioselective hydrogenation of carbon double-bonds, degradation of the steroid C17 side-chain, ester hydrolysis and oxidative hydroxylation. In total, 41 TPs were tentatively identified and 22 of them were unambiguously confirmed via reference standards. Additionally, 12 TPs were detected in the effluents of municipal WWTPs and, to the best of our knowledge, the occurrence of eight of these TPs has been shown for the first time. These TPs might significantly contribute to the detected residual endocrine activities in the aquatic environments. Therefore, there is a strong need for efficient removal strategies, in particular for persistent steroid hormones with elevated potencies.


Assuntos
Glucocorticoides , Poluentes Químicos da Água , Biodegradação Ambiental , Cinética , Águas Residuárias
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