RESUMEN
BACKGROUND: Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease. METHODS: In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful). RESULTS: A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation. CONCLUSIONS: Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.).
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Oftalmopatía de Graves/tratamiento farmacológico , Receptor IGF Tipo 1/antagonistas & inhibidores , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Diplopía/tratamiento farmacológico , Método Doble Ciego , Esquema de Medicación , Exoftalmia/tratamiento farmacológico , Oftalmopatía de Graves/diagnóstico por imagen , Humanos , Análisis de Intención de Tratar , Imagen por Resonancia Magnética , Persona de Mediana Edad , Órbita/diagnóstico por imagen , Receptor IGF Tipo 1/inmunología , AutoinformeRESUMEN
BACKGROUND: Psoriasis is an autoimmune disease that affects approximately 100 million people worldwide, and is a disease that can be ameliorated by anti-cytokine treatment. We aimed to compare the efficacy and safety of risankizumab with adalimumab in patients with moderate-to-severe plaque psoriasis. METHODS: IMMvent was a phase 3, randomised, double-blind, active-comparator-controlled trial completed at 66 clinics in 11 countries. Eligible patients were aged 18 years or older with moderate-to-severe chronic plaque psoriasis. Patients were randomly assigned 1:1 using interactive response technology to receive 150 mg risankizumab subcutaneously at weeks 0 and 4 or 80 mg adalimumab subcutaneously at randomisation, then 40 mg at weeks 1, 3, 5, and every other week thereafter during a 16-week double-blind treatment period (part A). For weeks 16-44 (part B), adalimumab intermediate responders were re-randomised 1:1 to continue 40 mg adalimumab or switch to 150 mg risankizumab. In part A, participants and investigators were masked to study treatment. Randomisation was stratified by weight and previous tumour necrosis factor inhibitor exposure. Co-primary endpoints in part A were a 90% improvement from baseline (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16, and for part B was PASI 90 at week 44 (non-responder imputation). Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the safety population (all patients who received at least one dose of study drug or placebo). This study is registered with ClinicalTrials.gov, number NCT02694523. FINDINGS: Between March 31, 2016, and Aug 24, 2017, 605 patients were randomly assigned to receive either risankizumab (n=301, 50%) or adalimumab (n=304, 50%). 294 (98%) of patients in the risankizumab group and 291 (96%) in the adalimumab group completed part A, and 51 (96%) of 53 patients re-randomised to risankizumab and 51 (91%) of 56 patients re-randomised to continue adalimumab completed part B. At week 16, PASI 90 was achieved in 218 (72%) of 301 patients given risankizumab and 144 (47%) of 304 patients given adalimumab (adjusted absolute difference 24·9% [95% CI 17·5-32·4]; p<0·0001), and sPGA scores of 0 or 1 were achieved in 252 (84%) patients given risankizumab and 252 (60%) patients given adalimumab (adjusted absolute difference 23·3% [16·6-30·1]; p<0·0001). In part B, among adalimumab intermediate responders, PASI 90 was achieved by 35 (66%) of 53 patients switched to risankizumab and 12 (21%) of 56 patients continuing adalimumab (adjusted absolute difference 45·0% [28·9-61·1]; p<0·0001) at week 44. Adverse events were reported in 168 (56%) of 301 patients given risankizumab and 179 (57%) of 304 patients given adalimumab in part A, and among adalimumab intermediate responders, adverse events were reported in 40 (75%) of 53 patients who switched to risankizumab and 37 (66%) of 56 patients who continued adalimumab in part B. INTERPRETATION: Risankizumab showed significantly greater efficacy than adalimumab in providing skin clearance in patients with moderate-to-severe plaque psoriasis. No additional safety concerns were identified for patients who switched from adalimumab to risankizumab. Treatment with risankizumab provides flexibility in the long-term treatment of psoriasis. FUNDING: AbbVie and Boehringer Ingelheim.
Asunto(s)
Adalimumab/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Psoriasis/tratamiento farmacológico , Adalimumab/efectos adversos , Adulto , Anticuerpos Monoclonales/efectos adversos , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Risankizumab is a humanised IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23, inhibiting this key cytokine and its role in psoriatic inflammation. We aimed to assess the efficacy and safety of risankizumab compared with placebo or ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. METHODS: UltIMMa-1 and UltIMMa-2 were replicate phase 3, randomised, double-blind, placebo-controlled and active comparator-controlled trials done at 139 sites in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain, and the USA. Eligible patients were 18 years or older, with moderate-to-severe chronic plaque psoriasis. In each study, patients were stratified by weight and previous exposure to tumour necrosis factor inhibitor and randomly assigned (3:1:1) by use of interactive response technology to receive 150 mg risankizumab, 45 mg or 90 mg ustekinumab (weight-based per label), or placebo. Following the 16-week double-blind treatment period (part A), patients initially assigned to placebo switched to 150 mg risankizumab at week 16; other patients continued their originally randomised treatment (part B, double-blind, weeks 16-52). Study drug was administered subcutaneously at weeks 0 and 4 during part A and at weeks 16, 28, and 40 during part B. Co-primary endpoints were proportions of patients achieving a 90% improvement in the Psoriasis Area Severity Index (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16 (non-responder imputation). All efficacy analyses were done in the intention-to-treat population. These trials are registered with ClinicalTrials.gov, numbers NCT02684370 (UltIMMa-1) and NCT02684357 (UltIMMa-2), and have been completed. FINDINGS: Between Feb 24, 2016, and Aug 31, 2016, 506 patients in UltIMMa-1 were randomly assigned to receive 150 mg risankizumab (n=304), 45 mg or 90 mg ustekinumab (n=100), or placebo (n=102). Between March 1, 2016, and Aug 30, 2016, 491 patients in UltIMMa-2 were randomly assigned to receive 150 mg risankizumab (n=294), 45 mg or 90 mg ustekinumab (n=99), or placebo (n=98). Co-primary endpoints were met for both studies. At week 16 of UltIMMa-1, PASI 90 was achieved by 229 (75·3%) patients receiving risankizumab versus five (4·9%) receiving placebo (placebo-adjusted difference 70·3% [95% CI 64·0-76·7]) and 42 (42·0%) receiving ustekinumab (ustekinumab-adjusted difference 33·5% [22·7-44·3]; p<0·0001 vs placebo and ustekinumab). At week 16 of UltIMMa-2, PASI 90 was achieved by 220 (74·8%) patients receiving risankizumab versus two (2·0%) receiving placebo (placebo-adjusted difference 72·5% [95% CI 66·8-78·2]) and 47 (47·5%) receiving ustekinumab (ustekinumab-adjusted difference 27·6% [16·7-38·5]; p<0·0001 vs placebo and ustekinumab). In UltIMMa-1, sPGA 0 or 1 at week 16 was achieved by 267 (87·8%) patients receiving risankizumab versus eight (7·8%) receiving placebo (placebo-adjusted difference 79·9% [95% CI 73·5-86·3]) and 63 (63·0%) receiving ustekinumab (ustekinumab-adjusted difference 25·1% [15·2-35·0]; p<0·0001 vs placebo and ustekinumab). In UltIMMa-2, 246 (83·7%) patients receiving risankizumab versus five (5·1%) receiving placebo (placebo-adjusted difference 78·5% [95% CI 72·4-84·5]) and 61 (61·6%) receiving ustekinumab achieved sPGA 0 or 1 at week 16 (ustekinumab-adjusted difference 22·3% [12·0-32·5]; p<0·0001 vs placebo and ustekinumab). The frequency of treatment-emergent adverse events in UltIMMa-1 and UltIMMa-2 was similar across risankizumab (part A: 151 [49·7%] of 304 and 134 [45·6%] of 294; part B: 182 [61·3%] of 297 and 162 [55·7%] of 291), placebo (part A: 52 [51·0%] of 102 and 45 [45·9%] of 98), ustekinumab (part A: 50 [50·0%] of 100 and 53 [53·5%] of 99; part B: 66 [66·7%] of 99 and 70 [74·5%] of 94), and placebo to risankizumab (part B: 65 [67·0%] of 97 and 61 [64·9%] of 94) treatment groups throughout the study duration. INTERPRETATION: Risankizumab showed superior efficacy to both placebo and ustekinumab in the treatment of moderate-to-severe plaque psoriasis. Treatment-emergent adverse event profiles were similar across treatment groups and there were no unexpected safety findings. FUNDING: AbbVie and Boehringer Ingelheim.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Fármacos Dermatológicos/farmacología , Psoriasis/tratamiento farmacológico , Ustekinumab/farmacología , Adulto , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Inmunoglobulina G/uso terapéutico , Inyecciones Subcutáneas/métodos , Interleucina-12/metabolismo , Subunidad p19 de la Interleucina-23/efectos de los fármacos , Subunidad p19 de la Interleucina-23/metabolismo , Masculino , Persona de Mediana Edad , Placebos , Psoriasis/etnología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismo , Ustekinumab/administración & dosificación , Ustekinumab/efectos adversosRESUMEN
BACKGROUND: In this phase 2, randomized, double-blind, placebo-controlled, dose-ranging study, we assessed the efficacy and safety of brodalumab (AMG 827), a human anti-interleukin-17-receptor monoclonal antibody, for the treatment of moderate-to-severe plaque psoriasis. METHODS: We randomly assigned patients with a score of 12 or higher on the psoriasis area-and-severity index (PASI, on which scores range from 0 to 72, with higher scores indicating more severe disease) and with 10% or more of their body-surface area affected by psoriasis to receive brodalumab (70 mg, 140 mg, or 210 mg at day 1 and weeks 1, 2, 4, 6, 8, and 10 or 280 mg monthly) or placebo. The primary end point was the percentage improvement from baseline in the PASI score at week 12. Secondary end points included improvement of at least 75% and at least 90% in the PASI score and the score on the static physician's global assessment at week 12. RESULTS: A total of 198 patients underwent randomization. At week 12, the mean percentage improvements in the PASI score were 45.0% among patients receiving 70 mg of brodalumab, 85.9% among those receiving 140 mg, 86.3% among those receiving 210 mg, 76.0% among those receiving 280 mg, and 16.0% among those receiving placebo (P<0.001 for all comparisons with placebo). An improvement of at least 75% and at least 90% in the PASI score at week 12 was seen in 77% and 72%, respectively, of the patients in the 140-mg brodalumab group and in 82% and 75%, respectively, of the patients in the 210-mg group, as compared with 0% in the placebo group (P<0.001 for all comparisons). The percentage of patients with a static physician's global assessment of clear or minimal disease was 26%, 85%, 80%, and 69% with the 70-mg, 140-mg, 210-mg, and 280-mg doses, respectively, of brodalumab, as compared with 3% with placebo (P<0.01 for all comparisons with placebo). Two cases of grade 3 neutropenia were reported in the 210-mg brodalumab group. The most commonly reported adverse events in the combined brodalumab groups were nasopharyngitis (8%), upper respiratory tract infection (8%), and injection-site erythema (6%). CONCLUSIONS: Brodalumab significantly improved plaque psoriasis in this 12-week, phase 2 study. (Funded by Amgen; ClinicalTrials.gov number, NCT00975637.).
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Psoriasis/tratamiento farmacológico , Receptores de Interleucina-17/inmunología , Adulto , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Receptores de Interleucina-17/antagonistas & inhibidores , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Mucormycosis is a fungal infection caused by environmentally acquired molds. We investigated a cluster of cases of cutaneous mucormycosis among persons injured during the May 22, 2011, tornado in Joplin, Missouri. METHODS: We defined a case as a soft-tissue infection in a person injured during the tornado, with evidence of a mucormycete on culture or immunohistochemical testing plus DNA sequencing. We conducted a case-control study by reviewing medical records and conducting interviews with case patients and hospitalized controls. DNA sequencing and whole-genome sequencing were performed on clinical specimens to identify species and assess strain-level differences, respectively. RESULTS: A total of 13 case patients were identified, 5 of whom (38%) died. The patients had a median of 5 wounds (range, 1 to 7); 11 patients (85%) had at least one fracture, 9 (69%) had blunt trauma, and 5 (38%) had penetrating trauma. All case patients had been located in the zone that sustained the most severe damage during the tornado. On multivariate analysis, infection was associated with penetrating trauma (adjusted odds ratio for case patients vs. controls, 8.8; 95% confidence interval [CI], 1.1 to 69.2) and an increased number of wounds (adjusted odds ratio, 2.0 for each additional wound; 95% CI, 1.2 to 3.2). Sequencing of the D1-D2 region of the 28S ribosomal DNA yielded Apophysomyces trapeziformis in all 13 case patients. Whole-genome sequencing showed that the apophysomyces isolates were four separate strains. CONCLUSIONS: We report a cluster of cases of cutaneous mucormycosis among Joplin tornado survivors that were associated with substantial morbidity and mortality. Increased awareness of fungi as a cause of necrotizing soft-tissue infections after a natural disaster is warranted.
Asunto(s)
Dermatomicosis/etiología , Fascitis Necrotizante/etiología , Mucorales/aislamiento & purificación , Mucormicosis/etiología , Infecciones de los Tejidos Blandos/etiología , Tornados , Heridas y Lesiones/complicaciones , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , ADN de Hongos/análisis , ADN Ribosómico , Dermatomicosis/epidemiología , Dermatomicosis/mortalidad , Desastres , Fascitis Necrotizante/epidemiología , Fascitis Necrotizante/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Missouri/epidemiología , Mucorales/clasificación , Mucorales/genética , Mucormicosis/epidemiología , Mucormicosis/mortalidad , Factores de Riesgo , Piel/lesiones , Infecciones de los Tejidos Blandos/epidemiología , Infecciones de los Tejidos Blandos/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Novel therapies are needed for difficult-to-treat populations of patients with psoriasis. OBJECTIVE: We sought to assess the efficacy and safety of the interleukin-17 Receptor A inhibitor brodalumab in patients with psoriasis with or without a self-reported history of psoriatic arthritis (PsA) and with or without a history of biologic use. METHODS: Subset analyses of a phase II, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis were performed. Improvement from baseline in Psoriasis Area and Severity Index score of 75%, 90%, and 100% at week 12; static Physician Global Assessment (0/1) score; Dermatology Life Quality Index response; and Psoriasis Symptom Inventory response were evaluated within subgroups. RESULTS: Efficacy and quality-of-life measures were generally similar between subgroups of patients with or without a history of PsA and with or without a history of biologic use across brodalumab doses and were significantly higher among patients who received brodalumab 140 mg every 2 weeks or 210 mg every 2 weeks versus placebo. LIMITATIONS: Differences between subgroups were not compared statistically, PsA was self-reported, only skin involvement/symptoms were reported, and reasons for discontinuation of prior biologic were not captured. CONCLUSION: Brodalumab is efficacious in patients with psoriasis with or without a history of PsA or biologic use.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Artritis Psoriásica/tratamiento farmacológico , Método Doble Ciego , Humanos , Índice de Severidad de la EnfermedadRESUMEN
Infections caused by Penicillium species are rare in dogs, and the prognosis in these cases is poor. An unknown species of Penicillium was isolated from a bone lesion in a young dog with osteomyelitis of the right ilium. Extensive diagnostic evaluation did not reveal evidence of dissemination. Resolution of lameness and clinical stability of disease were achieved with intravenous phospholipid-complexed amphotericin B initially, followed by long-term combination therapy with terbinafine and ketoconazole. A detailed morphological and molecular characterization of the mold was undertaken. Sequence analysis of the internal transcribed spacer revealed the isolate to be closely related to Penicillium menonorum and Penicillium pimiteouiense. Additional sequence analysis of ß-tubulin, calmodulin, minichromosome maintenance factor, DNA-dependent RNA polymerase, and pre-rRNA processing protein revealed the isolate to be a novel species; the name Penicillium canis sp. nov. is proposed. Morphologically, smooth, ovoid conidia, a greenish gray colony color, slow growth on all media, and a failure to form ascomata distinguish this species from closely related Penicillium species.
Asunto(s)
Enfermedades de los Perros/microbiología , Osteomielitis/veterinaria , Penicillium/clasificación , Penicillium/aislamiento & purificación , Anfotericina B/uso terapéutico , Animales , Antifúngicos/uso terapéutico , Análisis por Conglomerados , ADN de Hongos/química , ADN de Hongos/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Enfermedades de los Perros/tratamiento farmacológico , Perros , Femenino , Proteínas Fúngicas/genética , Histocitoquímica , Cetoconazol/uso terapéutico , Datos de Secuencia Molecular , Naftalenos/uso terapéutico , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Penicillium/genética , Filogenia , Radiografía Abdominal , Análisis de Secuencia de ADN , Terbinafina , Resultado del TratamientoRESUMEN
We describe a case of paravertebral abscess caused by a Phellinus sp. in a boy with chronic granulomatous disease. Sequence-based identification of this mold, a new agent of disease, suggests a close relation to Phellinus umbrinellus.
Asunto(s)
Absceso/diagnóstico , Absceso/microbiología , Basidiomycota/aislamiento & purificación , Enfermedad Granulomatosa Crónica/complicaciones , Micosis/diagnóstico , Micosis/microbiología , Absceso/patología , Antifúngicos/farmacología , Basidiomycota/clasificación , Basidiomycota/efectos de los fármacos , Basidiomycota/genética , Niño , Análisis por Conglomerados , ADN de Hongos/química , ADN de Hongos/genética , ADN Ribosómico/química , ADN Ribosómico/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Genes de ARNr , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Micosis/patología , Filogenia , ARN de Hongos/genética , ARN Ribosómico/genética , Radiografía Abdominal , Radiografía Torácica , Análisis de Secuencia de ADN , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Brodalumab (anti-interleukin-17-receptor antibody) was effective in treating moderate to severe psoriasis in a 12-week, dose-ranging, placebo-controlled trial. OBJECTIVE: We sought to evaluate efficacy and safety of long-term brodalumab treatment. METHODS: In this interim analysis at week 120 of an open-label extension study, patients received brodalumab 210 mg every 2 weeks. Protocol amendments reduced the dose (140 mg) in patients weighing 100 kg or less and subsequently increased the dose (210 mg) in patients with inadequate responses. Efficacy was measured by static physician global assessment and 75% or greater, 90% or greater, or 100% improvement in Psoriasis Area and Severity Index score (PASI-75, PASI-90, and PASI-100, respectively). RESULTS: Of 181 patients, 144 completed week 120. Static physician global assessment scores of clear/almost clear and clear were achieved by 90% and 63% of patients, respectively, at week 12 and by 72% and 51% at week 120. The PASI-75, PASI-90, and PASI-100 response rates at week 12 (95%/85%/63%) were sustained through week 120 (86%/70%/51%). Most commonly reported adverse events were nasopharyngitis (26.5%), upper respiratory tract infection (19.9%), arthralgia (16.0%), and back pain (11.0%). Four patients had grade-2 absolute neutrophil count. LIMITATIONS: There was no control group in this open-label extension. CONCLUSION: Brodalumab demonstrated sustained clinical response and an acceptable safety profile through 120 weeks in patients with moderate to severe psoriasis.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Psoriasis/tratamiento farmacológico , Receptores de Interleucina-17/antagonistas & inhibidores , Adulto , Anticuerpos Monoclonales Humanizados , Ensayos Clínicos Controlados como Asunto , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/inmunología , Receptores de Interleucina-17/inmunología , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Stachybotrys eucylindrospora was characterised as a new species in 2007, and we present the first report of this organism isolated from foreign material recovered from a patient. It is probable that isolates of this species have been previously identified as either Stachybotrys chartarum or Stachybotrys cylindrospora.
Asunto(s)
Cuerpos Extraños en el Ojo/microbiología , Lesiones Oculares/microbiología , Stachybotrys/aislamiento & purificación , Niño , Humanos , Masculino , Datos de Secuencia Molecular , Stachybotrys/clasificaciónRESUMEN
Triadelphia pulvinata is a rare dematiaceous fungus found in soil. We report the first case of invasive disease in a patient with acute myeloid leukemia who had a bloodstream infection with possibly both lung and brain involvement. Identification was by combined phenotypic features and fungal ribosomal DNA sequence analysis.
Asunto(s)
Ascomicetos/aislamiento & purificación , Fungemia/diagnóstico , Fungemia/patología , Leucemia Mieloide Aguda/complicaciones , Ascomicetos/clasificación , Ascomicetos/genética , Infecciones Fúngicas del Sistema Nervioso Central/complicaciones , Infecciones Fúngicas del Sistema Nervioso Central/diagnóstico , Infecciones Fúngicas del Sistema Nervioso Central/microbiología , Infecciones Fúngicas del Sistema Nervioso Central/patología , ADN de Hongos/química , ADN de Hongos/genética , ADN Ribosómico/química , ADN Ribosómico/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Femenino , Fungemia/complicaciones , Fungemia/microbiología , Humanos , Enfermedades Pulmonares Fúngicas/complicaciones , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedades Pulmonares Fúngicas/microbiología , Enfermedades Pulmonares Fúngicas/patología , Microscopía , Persona de Mediana Edad , Datos de Secuencia Molecular , Radiografía Torácica , Análisis de Secuencia de ADN , Tomografía Computarizada por Rayos XRESUMEN
Prepatellar bursitis is typically a monomicrobial bacterial infection. A fungal cause is rarely identified. We describe a 61-year-old man who had received a renal transplant 21 months prior to presentation whose synovial fluid and surgical specimens grew Phomopsis bougainvilleicola, a pycnidial coelomycete.
Asunto(s)
Ascomicetos , Bursitis/microbiología , Trasplante de Riñón , Traumatismos de la Rodilla/microbiología , Micosis/microbiología , Ascomicetos/clasificación , Ascomicetos/genética , Ascomicetos/crecimiento & desarrollo , Bursitis/diagnóstico , ADN Bacteriano , Humanos , Trasplante de Riñón/efectos adversos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Micosis/diagnóstico , Filogenia , UltrasonografíaRESUMEN
Rasamsonia argillacea (formerly known as Geosmithia argillacea) is a fungus recently recognized as a pathogen of immunocompromised patients. Here we report the first case of Rasamsonia infection in an immunocompetent host, presenting as a pulmonary and aortic graft infection. Its morphological similarity to nonpathogenic Penicillium species delayed the diagnosis and initiation of appropriate treatment.
Asunto(s)
Aortitis/microbiología , Eurotiales , Huésped Inmunocomprometido , Enfermedades Pulmonares Fúngicas/microbiología , Aortitis/diagnóstico , Bronquiectasia/microbiología , Bronquiectasia/patología , Eurotiales/clasificación , Eurotiales/citología , Eurotiales/genética , Genes Bacterianos , Humanos , Enfermedades Pulmonares Fúngicas/diagnóstico , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Tomografía Computarizada por Rayos XRESUMEN
We describe an opportunistic, disseminated infection in a German shepherd dog associated with two fungal organisms not previously reported to cause disease. Lecythophora canina, a new species here described, was isolated from an osteolytic bone lesion. A fine needle aspirate of the lesion demonstrated septate hyphae. Plectospharella cucumerina (anamorph Plectosporium tabacinum) was isolated from a urine sample. Clinical manifestations were blindness, altered mentation, and osteomyelitis. Treatment with itraconazole and terbinafine for greater than one year resulted in stable clinical disease.
Asunto(s)
Ascomicetos/clasificación , Ascomicetos/aislamiento & purificación , Coinfección/veterinaria , Enfermedades de los Perros/microbiología , Micosis/veterinaria , Animales , Ascomicetos/genética , Biopsia con Aguja Fina , Huesos/diagnóstico por imagen , Coinfección/microbiología , ADN de Hongos/química , ADN de Hongos/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Perros , Microscopía , Datos de Secuencia Molecular , Micosis/microbiología , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/veterinaria , Osteomielitis/microbiología , Osteomielitis/veterinaria , Radiografía , Análisis de Secuencia de ADN , Orina/microbiologíaRESUMEN
BACKGROUND: Few clinical trials have evaluated the combination of topical corticosteroids plus systemic therapies for psoriasis. OBJECTIVE: We sought to evaluate efficacy and safety of etanercept plus topical clobetasol propionate (CP) foam versus etanercept monotherapy for treatment of moderate to severe plaque psoriasis. METHODS: Adults with Psoriasis Area and Severity Index (PASI) score greater than or equal to 10 and psoriasis-affected body surface area greater than or equal to 10% were randomized to etanercept with CP as needed to clear (2 up-to-2-week courses, weeks 11-12 and 23-24) or etanercept alone (each arm at 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks). RESULTS: A total of 592 patients enrolled (295 etanercept + CP arm; 297 etanercept arm). At week 12, significant differences were observed for response of 75% improvement in PASI score (primary end point, 65.2% vs 48.3% in the etanercept + CP vs etanercept arms, respectively; P < .001), response of 90% improvement in PASI score (29.7% vs 19.4%; P = .009), percentage PASI score improvement (76.5% vs 68.2%; P < .001), static physician global assessment of clear/almost clear (63.1% vs 47.3%; P < .001), and patient satisfaction with treatment (P = .006). Response of 75% improvement in PASI score and static physician global assessment of clear/almost clear were not significantly different between arms at week 24. Patient satisfaction with treatment (P = .001) and percentage improvement in PASI score (P = .031) were also greater in the etanercept + CP arm compared with etanercept only at week 24. Comparable numbers of adverse events occurred in each arm. LIMITATIONS: No placebo for CP foam was provided in the etanercept arm. CONCLUSIONS: Addition of CP to etanercept yielded increased efficacy compared with etanercept alone at week 12 without an increase in treatment-related adverse events.
Asunto(s)
Antiinflamatorios/uso terapéutico , Clobetasol/uso terapéutico , Inmunoglobulina G/uso terapéutico , Psoriasis/tratamiento farmacológico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Administración Cutánea , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Superficie Corporal , Clobetasol/administración & dosificación , Quimioterapia Combinada , Etanercept , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Apophysomyces variabilis is an emerging fungal pathogen that can cause significant infections in immunocompetent patients. We report a case of A. variabilis invasive wound infection in a 21-year-old male after a self-inflicted burn injury.
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Quemaduras/complicaciones , Mucorales/aislamiento & purificación , Mucormicosis/diagnóstico , Mucormicosis/microbiología , Infección de Heridas/diagnóstico , Infección de Heridas/microbiología , ADN de Hongos/química , ADN de Hongos/genética , Histocitoquímica , Humanos , Masculino , Microscopía , Datos de Secuencia Molecular , Mucorales/citología , Mucorales/genética , Mucormicosis/patología , Análisis de Secuencia de ADN , Piel/patología , Infección de Heridas/patología , Adulto JovenRESUMEN
Paraconiothyrium cyclothyrioides is a recently described coelomycetous fungal species. We present a case in a renal transplant patient with chronic skin lesions of the lower extremities caused by P. cyclothyrioides. Treatment with posaconazole led to complete resolution of the lesions. P. cyclothyrioides should be considered an opportunistic human pathogen in immunocompromised patients.
Asunto(s)
Ascomicetos/aislamiento & purificación , Feohifomicosis/diagnóstico , Feohifomicosis/patología , Antifúngicos/administración & dosificación , Ascomicetos/clasificación , Ascomicetos/genética , ADN de Hongos/química , ADN de Hongos/genética , Humanos , Huésped Inmunocomprometido , Trasplante de Riñón , Extremidad Inferior/patología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Feohifomicosis/tratamiento farmacológico , Feohifomicosis/microbiología , Análisis de Secuencia de ADN , Trasplante , Resultado del Tratamiento , Triazoles/administración & dosificaciónRESUMEN
We report progressive necrotizing fungal cellulitis and myositis in the leg of a patient with glioblastoma multiforme treated with temozolomide and corticosteroids. While the morphologic appearance of the isolate and its ability to grow at temperatures greater than 32°C were suggestive of Mycoleptodiscus indicus, some of the conidia were atypical for this species in that they had single septa and occasional lateral appendages. Furthermore, the isolate was different from M. indicus based on the sequencing analysis of two rDNA regions. This is the first case of Mycoleptodiscus invasive fungal disease in which the causative agent could not be resolved at the species level because of inconsistencies between morphological and molecular data.
Asunto(s)
Ascomicetos/aislamiento & purificación , Celulitis (Flemón)/diagnóstico , Celulitis (Flemón)/microbiología , Micosis/diagnóstico , Micosis/microbiología , Miositis/diagnóstico , Miositis/microbiología , Corticoesteroides/administración & dosificación , Adulto , Antiinflamatorios/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Celulitis (Flemón)/complicaciones , Celulitis (Flemón)/patología , Análisis por Conglomerados , ADN de Hongos/química , ADN de Hongos/genética , ADN Ribosómico/química , ADN Ribosómico/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Dacarbazina/administración & dosificación , Dacarbazina/análogos & derivados , Glioblastoma/complicaciones , Glioblastoma/tratamiento farmacológico , Humanos , Pierna/patología , Masculino , Datos de Secuencia Molecular , Micosis/complicaciones , Micosis/patología , Miositis/complicaciones , Miositis/patología , Filogenia , Análisis de Secuencia de ADN , TemozolomidaRESUMEN
BACKGROUND: Infertility often is a dyadic stressor that constitutes blockage of a major life goal. PURPOSE: This study's primary aims were to examine heterosexual partners' goal appraisals during treatment for infertility and to test whether the direct effects of and interactions between partners' goal-related perceptions were associated with each partner's adjustment. METHOD: Women (n = 37) receiving fertility treatment and their male partners (n = 37) completed measures of goal appraisal and psychological adjustment. RESULTS: Partners did not differ on ratings of the importance of the goal of parenthood, but women indicated lower perceived chance of becoming pregnant and higher perceived goal blockage than their partners. Goal appraisals were moderately correlated between partners and uncorrelated with the number of treatment procedures undergone by the couple. Women reported greater depressive symptoms, more infertility-specific thought intrusion, and lower positive states of mind than their partners. Women's appraisal of greater likelihood of becoming pregnant was psychologically protective, but greater perceived likelihood of becoming pregnant reported by their partners was associated with women's negative psychological adjustment. CONCLUSION: Examining the associations between couples' goal appraisals and psychological adjustment may aid in developing targeted interventions to promote psychological adjustment to infertility. The small sample may have prevented identifying interactions between partners' goal assessment measures.