Risk of invasive fungal infections among patients treated with disease modifying treatments for multiple sclerosis: a comprehensive review.

Introduction: Disease modifying treatments are commonly used in the treatment of multiple sclerosis. As different opportunistic infections have been reported, concerns are also raised regarding the risk of invasive fungal infections.Areas covered: Both clinical trials and observational studies on safety and efficacy of diseases modifying treatment for multiple sclerosis were reviewed and data regarding the occurrence of invasive fungal infections were reported. Papers evaluating the following drugs were reviewed: rituximab, ocrelizumab, alemtuzumab, fingolimod, natalizumab, dimethyl fumarate, interferon, glatiramer acetate, cladribine, teriflunomide.Expert opinion: Overall, the occurrence of invasive fungal infections was low, with most infective events reported among patients treated with monoclonal antibodies and fingolimod. Aspergillosis and cryptococcal meningitidis were the most representative fungal infections. Although not common, these infections may be difficult to diagnose and their fatality rate is often high. For this reason, screening protocols for fungal infections must be implemented in the clinical practice when managing patients with MS.

Immunoglobulin G responses to a panel of Candida albicans antigens as accurate and early markers for the presence of systemic candidiasis.

Despite shortcomings, cultures of blood and sterile sites remain the "gold standard" for diagnosing systemic candidiasis. Alternative diagnostic markers, including antibody detection, have been developed, but none are widely accepted. In this study, we used an enzyme-linked immunosorbent assay to measure serum antibody responses against 15 recombinant Candida albicans antigens among 60 patients with systemic candidiasis due to various Candida spp. and 24 uninfected controls. Mean immunoglobulin G (IgG) responses against all 15 antigens were significantly higher among patients with systemic candidiasis than among controls, whereas IgM responses were higher against only seven antigens. Using discriminant analysis that included IgG responses against the 15 antigens, we derived a mathematical prediction model that identified patients with systemic candidiasis with an error rate of 3.7%, a sensitivity of 96.6%, and a specificity of 95.6%. Furthermore, a prediction model using a subset of four antigens (SET1, ENO1, PGK1-2, and MUC1-2) identified through backward elimination and canonical correlation analyses performed as accurately as the full panel. Using the simplified model, we predicted systemic candidiasis in a separate test sample of 32 patients and controls with 100% sensitivity and 87.5% specificity. We also demonstrated that IgG titers against each of the four antigens included in the prediction model were significantly higher in convalescent-phase sera than in paired acute-phase sera. Taken together, our findings suggest that IgG responses against a panel of candidal antigens might represent an accurate and early marker of systemic candidiasis, a hypothesis that should be tested in future trials.

Avaliação dos resultados clínicos após cirurgia descompressiva em cães com doença de disco intervertebral

Clinical results after decompressive surgery were evaluated in 45 dogs with cervical or thoracolumbar intervertebral disk disease. After surgery, 35 dogs recovered totally, eight (17.8%) partially, and two (4.4%) did not present any change in clinical findings. Eight dogs with paraplegy and loss of deep pain perception showed improvement, with total recovering in 62.5% of cases. Surgery was effective in four dogs with tetraparesy. Decompressive surgery (cervical slot or hemilaminectomy), with removal of disk material from inside the vertebral canal, was an effective form to produce functional improvement in dogs with this disease.

Avaliaram-se os resultados clínicos após realização de cirurgia descompressiva em 45 cães com doença do disco intervertebral cervical ou toracolombar. Após a cirurgia, 35 cães (77,8%) recuperaram-se totalmente, oito (17,8%) parcialmente e dois (4,4%) não apresentaram alteração do quadro inicial. Em oito cães com paraplegia e perda da sensibilidade dolorosa profunda houve completa melhora do quadro clínico, com recuperação total em 62,5% dos casos. Em quatro cães com tetraparesia, a cirurgia foi eficaz. A cirurgia descompressiva (slot cervical e hemilaminectomia toracolombar), com a retirada do material do disco do interior do canal vertebral, foi uma forma efetiva de gerar melhora do quadro funcional.

Avaliação dos resultados clínicos após cirurgia descompressiva em cães com doença de disco intervertebral / Evaluation of clinical results of decompressive surgery in dogs with degenerative disk disease

Avaliaram-se os resultados clínicos após realização de cirurgia descompressiva em 45 cães com doença do disco intervertebral cervical ou toracolombar. Após a cirurgia, 35 cães (77,8 por cento) recuperaram-se totalmente, oito (17,8 por cento) parcialmente e dois (4,4 por cento) não apresentaram alteração do quadro inicial. Em oito cães com paraplegia e perda da sensibilidade dolorosa profunda houve completa melhora do quadro clínico, com recuperação total em 62,5 por cento dos casos. Em quatro cães com tetraparesia, a cirurgia foi eficaz. A cirurgia descompressiva (slot cervical e hemilaminectomia toracolombar), com a retirada do material do disco do interior do canal vertebral, foi uma forma efetiva de gerar melhora do quadro funcional

Clinical results after decompressive surgery were evaluated in 45 dogs with cervical or thoracolumbar intervertebral disk disease. After surgery, 35 dogs recovered totally, eight (17.8 percent) partially, and two (4.4 percent) did not present any change in clinical findings. Eight dogs with paraplegy and loss of deep pain perception showed improvement, with total recovering in 62.5 percent of cases. Surgery was effective in four dogs with tetraparesy. Decompressive surgery (cervical slot or hemilaminectomy), with removal of disk material from inside the vertebral canal, was an effective form to produce functional improvement in dogs with this disease

Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary aspergillosis among solid-organ transplant recipients.

We review the experience at our institution with galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid in the diagnosis of invasive pulmonary aspergillosis (IPA) among solid-organ transplant recipients. Among 81 patients for whom BAL GM testing was ordered (heart, 24; kidney, 22; liver, 19; lung, 16), there were five cases of proven or probable IPA. All five patients had BAL GM of > or = 2.1 and survived following antifungal therapy. The sensitivity, specificity, and positive and negative predictive values for BAL GM testing at a cutoff of > or = 1.0 were 100%, 90.8%, 41.7%, and 100%, respectively. The sensitivity of BAL GM testing was better than that of conventional tests such as serum GM or BAL cytology and culture. Moreover, a positive BAL GM test diagnosed IPA several days to 4 weeks before other methods for three patients. Twelve patients had BAL GM of > or = 0.5 but no evidence of IPA. Among these, lung transplant recipients accounted for 41.7% (5/12) of the false-positive results, reflecting frequent colonization of airways in this population. Excluding lung transplants, the specificity and positive predictive value for other solid-organ transplants increased to 92.9% and 62.5%, respectively (cutoff, > or = 1.0). In conclusion, BAL GM testing facilitated more-rapid diagnoses of IPA and the institution of antifungal therapy among non-lung solid-organ transplant recipients and helped to rule out IPA.