RESUMO
Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among immunocompromised patients with underlying malignancies and prior transplants. FDA approved Isavuconazole as a primary therapy for Invasive Aspergillosis (IA) and Mucormycosis. This study aims to compare the real-world clinical outcomes and safety of isavuconazole to voriconazole and an amphotericin B-based regimen in patients with underlying malignancies and a transplant. In addition, the response to anti-fungal therapy and the outcome were compared among patients with a disparity (elderly, obese patients, patients with renal insufficiency and diabetes mellitus) versus those with no disparity. We performed a multicenter retrospective study, including patients with cancer diagnosed with an invasive fungal infection, and treated primarily with isavuconazole, voriconazole or amphotericin B. Clinical, radiologic findings, response to therapy and therapy related adverse events were evaluated during 12 weeks of follow-up. We included 112 patients aged 14 to 77 years, and most of the IFIs were classified into definite (29) or probable (51). Most cases were invasive aspergillosis (79%), followed by fusariosis (8%). Amphotericin B were used more frequently as primary therapy (38%) than isavuconazole (30%) or voriconazole (31%). Twenty one percent of the patients presented adverse events related to primary therapy, with patients receiving isavuconazole presenting less adverse events when compared to voriconazole and amphotericin (p < 0.001; p = 0.019). Favorable response to primary therapy during 12 weeks of follow-up were similar when comparing amphotericin B, isavuconazole or voriconazole use. By univariate analysis, the overall cause of mortality at 12 weeks was higher in patients receiving amphotericin B as primary therapy. However, by multivariate analysis, Fusarium infection, invasive pulmonary infection or sinus infection were the only independent risk factors associated with mortality. In the treatment of IFI for patients with underlying malignancy or a transplant, Isavuconazole was associated with the best safety profile compared to voriconazole or amphotericin B-based regimen. Regardless of the type of anti-fungal therapy used, invasive Fusarium infections and invasive pulmonary or sinus infections were the only risk factors associated with poor outcomes. Disparity criteria did not affect the response to anti-fungal therapy and overall outcome, including mortality.
RESUMO
The search for biomarkers that can help to establish an early diagnosis and prognosis of interstitial lung disease (ILD) is of potential interest. VEGF polymorphisms have been implicated in the development of several lung disorders. Consequently, we assessed, for the first time, the role of VEGF polymorphisms in the susceptibility and severity of ILD. A total of 436 Caucasian ILD patients (244 with idiopathic interstitial pneumonias (IIPs) and 192 with non-IIP) and 536 ethnically-matched healthy controls were genotyped for VEGF rs833061, rs1570360, rs2010963, rs3025020, and rs3025039 polymorphisms by TaqMan assays. Pulmonary function tests were collected from all the patients. VEGF serum levels were determined by ELISA in a subgroup of patients. No VEGF genotype, allele, carrier, or haplotype differences were found between ILD patients and controls as well as between IIP and non-IIP patients. However, an association of rs1570360 with IIP in women and also with lung function in IIP patients was found. None of the VEGF polymorphisms were associated with VEGF levels. In conclusion, our results suggest that VEGF does not seem to play a relevant role in ILD, although rs1570360 may influence the severity of ILD in women and a worse outcome in IIP patients.
