Background:Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by Paracoccidioides brasiliensis. Involvement of the central nervous system (CNS) occurs in about 10% of cases.Case Description:A 57-year-old white man presented with the complaint of headache and an episode of focal seizure 1 month earlier. Magnetic resonance imaging (MRI) revealed a ring-enhancing lesion in the right parietal lobe with peri-lesional vasogenic edema suggestive of a primary neoplasm. The patient underwent craniotomy and the intraoperative finding was a yellowish, hard lesion with thick content and yellow inside. Anatomo-pathological findings were pathognomonic of PCM: large, thick-walled, spherical yeast cells with multiple peripheral buds. The patient tested negative for human immunodeficiency virus (HIV). Encephalitis and meningitis were ruled out by cerebrospinal fluid analysis. Culture confirmed the diagnosis of PCM and the patient was treated with amphotericin B. The patient responded well to treatment with resolution of the headache and clinical improvement, despite a bitemporal hemianopia. He was clinically stable and then discharged in good general condition.Conclusions:Radiographic findings of PCM with CNS involvement may suggest neoplasia, making diagnosis difficult. In endemic areas, the diagnosis of PCM should be promptly considered when a ring-enhancing mass associated with peri-lesional edema is observed on MRI.

Less than 15% of patients with esophageal squamous cell carcinoma (ESCC) survive five years after the diagnosis. A better understanding of the biology of these tumors and the development of clinical biomarkers is necessary. Autophagy is a physiological mechanism involved in the turnover of cellular components, playing critical roles in cancer. In this study, we evaluated the differential levels of three major autophagy regulators (SQSTM1, MAP1LC3B, and BECN1) in ESCC patients. We associated autophagy with histopathologic features, including the differentiation grade, mitotic rate, inflammation score, and the intensity of tumor-infiltrating lymphocytes. We also assessed the nuclear morphometry of the tumor parenchyma and associated it with autophagy and histopathology. The three markers were significantly increased in ESCC in comparison to control. Based on the mean expression of each protein in the control group, 57% of ESCC patients showed high levels of the three markers, compared to 14% in controls. The most frequent profiles found in ESCC were BECNhigh/MAP1LC3high and BECNhigh/SQSTM1high. Using the TCGA database, we found that the autophagy is upregulated in ESCC. Furthermore, high levels of autophagy markers were associated with poor prognosis. Considering the nuclear morphometry, ESCC samples showed a significant reduction in nuclear area, which strongly correlated negatively with autophagy. Finally, the percentage of normal nuclei was associated with tumor differentiation, while lower levels of SQSTM1 were observed in poorly differentiated tumors. We found that the ESCC progression may involve an increase of autophagy and alterations in the nuclear structure, associated with clinically relevant histopathological features.

Background:Yellow Fever (YF) is an endemic disease, in specific areas of Brazil. Since 1942, no new urban cycle cases have been observed. Yet, in early 2017, outbreaks of YF were reported in many states, outside the endemic areas, where YF was not considered a risk. Hence, new and some fatal cases have been reported including in highly populated areas close to the city of São Paulo. As it has been widely broadcasted, population searching for vaccination significantly increased and cases of inadvertent vaccination have been registered.Objectives:To analyze the consequences of inadvertent YF primo-vaccination in patients with immune mediated inflammatory diseases (IMID).Methods:Observational study (12/2017–01/2018).54 rheumatologists from private practice at different areas of São Paulo included specific YF information in their patients’ orientations and actively searched for IMID patients that have received YF vaccination (YFV) inputting the data in a web-based questionnaire.Results:56 patients received YFV; female 42 (75%), mean (±SD) age= 56±14 yr, median disease duration= 7 yr (6 months-45 yr), Diagnosis: RA (n=39; 72%), PsA (n=5), AS (n=4), 2 SLE, 3 vasculitis, 2 SS, one ReA and 2 UA. Treatment: 30 (54%) were considered under current strong immunosuppression (CE≥20 mg, MTX>20 mg, leflunomide, tofacitinib and biologic agents (BA); 18 (32%) were on biologic agents (9 anti-TNF, 2 abatacept, 3 tocilizumab, 1 rituximab, 1 patient each secukinumab and tofacitinib). Remaining patients were receiving csDMARDs isolated or in combination, with or without low CE (≤10 mg).Vaccination: 54 (96%) cases were primo YFV and 43 (80%) related inadvertent YFV. Adverse events (AE): 7 patients (13%) had AE after a median of 4 days (hours-60 days);3 of them were on BA, corresponding to 17% of the total subjects on various BA. Severity of AE:4 patients had mild AE (local pain, vertigo, fever, headache, myalgia), in 2 of them, symptoms promptly resolved while 2 needed medical assistance (one was on tocilizumab). Of the 3 remaining cases, one had severe reaction one hour after YFV (probably anaphylaxis); Finally, 2 patients had severe AE requiring hospitalization: one had meningitis (RTX+MTX) and other (ADA+MTX), abdominal pain, myalgia, fever, headache, vertigo and increased liver enzymes. No fatal events were observed. Concerning the vaccine effect on disease activity, only 5 (9%) patients related worsening of the disease after YFV, but 2 of them also presented AE.Conclusions:The small number of reports precludes any conclusion about rate/severity of AE and YFV in immunosuppressed rheumatic patients. Nevertheless, it emphasized the necessary awareness and careful analysis of the risk-benefice of YFV in this population. The interference of YFV on IMID disease activity seems to be marginal. On the other hand, this descriptive analysis clearly demonstrated persistence of patient’s unfamiliarity with concepts of immunosuppression and its consequences, disclosing another unmet need in the management of patients with RD.Disclosure of Interes...