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Background: microRNAs (miRNAs) are directly associated with inflammatory response, but their direct role in CRSwNP (chronic rhinosinusitis with nasal polyps) remains evasive. This study aimed to compare the expression of several miRNAs in tissue samples obtained from patients with CRSwNP and controls and to evaluate if miRNAs correlate to a specific inflammatory pattern (T1, T2, T17, and Treg) or intensity of symptoms in CRSwNP. Methods: nasal polyps (from patients with CRSwNP – n=36) and middle turbinate mucosa (from control patients – n=41) were collected. Microarray determined human mature miRNA expression, and the results obtained were validated by qPCR. miRNAs that were differentially expressed were then correlated to cytokine proteins (by Luminex), tissue eosinophilia, and SNOT-22. Results: After microarray and qPCR analyses, six microRNAs were up-regulated in CRSwNP samples when compared with controls: miR-205-5p, miR-221-3p, miR-222-3p, miR-378a-3p, miR-449a and miR-449b-5p. All these miRNAs are directly implicated with cell cycle regulation and apoptosis, and to a minor extent, with inflammation. Importantly, miR-205-5p showed a significantly positive correlation with IL-5 concentration and eosinophil count at the tissue and with the worst SNOT-22 score. Conclusions: miRNA 205-5p was increased in CRSwNP compared to controls, and it was especially expressed in CRSwNP patients with higher T2 inflammation (measured by both IL-5 levels and local eosinophilia) and worst clinical presentation. This miRNA may be an interesting target to be explored in patients with CRSwNP.

Following burn, increased nitric oxide (NO) combine with superoxide anion forming peroxynitrite. Methylene blue (MB) has NO blocking and antioxidant effects. Male Wistar rats (250g) were burned bilaterally in dorsum with a comb metal plate heated inside boiling water and applied during 30s, creating four rectangular 10×20mm full-thickness burned areas separated by three 5×20mm unburned interspaces (stasis zone). 30 rats were randomized into three groups (n=10): treated groups received one dose of intraperitoneal (IP) MB injections (2mg/kg), one or six hours after injury, and control group received saline. Seven days after injury, wounds were visually analyzed for interspaces necrosis; full-thickness sections were evaluated with Masson staining; tissue fragments were processed for nitrite/nitrate (NOx) and malondialdehyde (MDA) dosages. Photographic analysis: interspaces progression to necrosis were higher in control (64.8%) than in one (44.7%) and six (13.3%) hours MB groups (P=0.0060). Histopathology showed lower necrosis percentage in one (34.85%) and six (41.62%) hours MB groups than control (77.03%) (P=0.0034) and higher normal skin percentage in one (25.33%) and six (26.85%) hours MB groups than control (8.32%) (P=0.0037). Re-epithelialization skin areas were higher in both MB groups (39.94% for one and 31.89% for six hours) than control (14.63%) (P=0.0210). Interspace's NOx increased in both MB groups (P=0.0130) with no difference in burned areas. No MDA difference was observed. IP MB injection one or six hours after injury reduced necrosis progression in stasis area in the rat comb burn model suggesting an antioxidant effect reducing oxidative stress.

Background The pathophysiology of chronic rhinosinusitis (CRS) is still not well known due to the multifactorial etiologies involved. Bacteria play a role in the pathogenesis of CRS by various means, including biofilm adhesion, intracellular persistence, or inducing inflammation secondary to toxins. Endotoxins and exotoxins, especially Staphylococcus aureus superantigens, can produce significant immune responses in the host and are implicated in patients with CRS. The majority of animal models described for CRS revalidates the pathophysiology of acute sinusitis, ostium occlusion, or foreign body associated infection. Objectives To evaluate an experimental model of eosinophilic CRS using prolonged exposure to bacterial toxins. The histological changes in rabbits exposed to S. aureus enterotoxin B (SEB), lipopolysaccharide (LPS), or lipoteichoic acid (LTA) were compared. Methods After induction with ovalbumin (OVA) sensitization with subcutaneous injection for 2 weeks, rabbits underwent surgery to insert an indwelling catheter into the maxillary sinus. The sinus was irrigated with OVA 3 times weekly for 2 weeks, followed by sinus irrigation with bacterial toxin (SEB: 1 µg/mL, LPS: 100 ng/mL, or LTA: 100 ng/mL) 3 times weekly for 4 weeks. The histological changes in the treated sinus were compared with control rabbits. Results Sinuses exposed to bacterial toxins (SEB, LPS, and LTA) produced significant mucosal thickening with infiltration of inflammatory cells, notably eosinophils. SEB was the only toxin that promoted a mixed pattern of inflammation, including eosinophilic and neutrophilic infiltration. Conclusion Our experimental model of eosinophilic CRS in rabbits produced significant mucosal thickening and inflammation in the sinuses exposed to bacterial toxins, with histological changes analogous to what is observed in patients with CRS with nasal polyps. This model may serve as a basis for future investigation of the pathogenesis of eosinophilic CRS in relation to bacterial toxins or as a model for testing new therapeutic modalities for this disease.

Background Early diagnosis of acute invasive fungal rhinosinusitis (AIFRS) is vital to improving outcomes in immunocompromised patients. This study evaluated the impact of a systematic protocol with nasal endoscopy and biopsies to early detect AIFRS in immunocompromised patients. Additionally, we compared the accuracy of frozen-section biopsy and culture with formalin-fixed paraffin-embedded (FFPE) biopsy. Methods Retrospective cohort in a Tertiary Referral Hospital. Patients with the suspected diagnosis of AIFRS were evaluated following a standardized protocol, including serial nasal endoscopies and biopsies when necessary. The sensitivity and specificity of frozen-section biopsy and culture were also compared with FFPE. Results The mortality rate related to AIFRS of this standardized cohort (13/43) was 30.2%. Better outcomes were observed in patients with disease limited to the turbinates and in those with higher peripheral neutrophils count. Frozen-section biopsy positivity correlated with FFPE findings for fungi detection (p-value

Background Dapsone hypersensitivity syndrome (DHS) is a rare, but potentially life-threatening reaction to dapsone. Objective Evaluation of immunological factors involved in the sparing of borderline-lepromatous (BL) leprosy patches by the severe exanthema related to DHS. Methods The authors describe a 19-year-old man with borderline-lepromatous leprosy with a recent diffuse rash, sparing only the hypochromic patches of leprosy, generalized lymphadenopathy, hepatomegaly, and jaundice 25 days after the start of multibacillary multidrug therapy. Results Laboratory testing was remarkable for leukocytosis with eosinophilia, atypical lymphocytosis, and elevated liver and canalicular enzymes. Immunohistopathology of the rash showed stronger expression of Th1 cytokines (IL1β, TNFα, IFNγ, and iNOS), and limited expression of IL17, TGFb, IL4, and IL10. Whereas the hypochromic leprosy patches showed high expression of inflammatory cytokines IL1β, TNFα, IFNγ, iNOS, and TGFβ (Th1), and presented strong expression of IL17 and TGFβ with no IL4 and IL10 expression, by the inflammatory infiltrate, characterizing a participation of Th17 response. Conclusion Th17 response, coupled with the presence of subepidermal collagen band, seems to be directly related to the absence of DHS rash in these hypochromic leprosy patches.

The present essay is aimed at describing the most characteristic imaging findings of mucinous carcinoma of the breast, with emphasis on the patterns related to better prognosis. The authors selected cases of mucinous carcinoma of the breast whose images were available, highlighting the imaging findings suggestive of this subtype of breast cancer, either at mammography, ultrasonography or magnetic resonance imaging. O objetivo deste artigo é descrever os aspectos de imagem mais característicos do carcinoma mucinoso de mama, destacando-se os padrões relacionados a melhor prognóstico. Foram selecionados casos de carcinoma mucinoso de mama enfatizando as características de imagem que sugiram esse subtipo de neoplasia mamária, seja na mamografia, ultrassonografia ou ressonância magnética.

CRS, a 48 years old male patient, presented with appro-ximately 30 years of bilateral nasal obstruction that was worse on the left, in addition to rhinorrhea, hyposmia, and difficulty sleeping. He denied cacosmia, headaches, and atopic or otological complaints. He also denied smoking or alcohol consumption, allergy to non-steroi-dal anti-inflammatory drugs, asthma, and other comor-bidities. Nasofibroscopic assessment disclosed a polypoid mass completely occluding the nasal cavity bilaterally. Computed tomography (CT) scan of the sinuses disclosed soft-tissue masses in both nasal cavities, larger on the left side, that extended to the choanae (Fig. 1A); bilateral enlargement of the ostiomeatal complex; partial opacification of the cells of the maxillary, ethmoid, and frontal sinuses; and left sphenoid mucosal thickening.Surgery was performed exclusively by nasal endoscopy. The intraoperative findings were limited to a single large polypoid mass in each nostril, arising from the medial wall of the maxillary sinus and extending to each choana; a right middle concha bullosa; edema, and retained secretions in the anterior and posterior ethmoid cells. Pathological assessment showed a 5.0 × 2.0 × 1.0 cm polypoid lesion on the right and a 5.0 × 2.5 × 1.0 cm on the left, covered by respiratory epithelium without goblet cell hyperplasia or basal membrane thickening, with grade 3 edema and grade 1 fibrosis of the stroma, discrete mixed infiltrate with a neutrophile count of four per field and four to six eosinophils per field, with no signs of malignan-cy, consistent with the diagnostic impression of antrocho-anal polyps (Fig. 1B). The patient experienced a complete recovery with resolution of complaints and no recurrence four months postoperatively.

Invasive lobular carcinoma (ILC) and lobular neoplasia (LN) are two distinct conditions that still pose challenges regarding to their classification, diagnosis and management. Although they share similar cellular characteristics, such as discohesive neoplastic cells and absence of e-cadherin staining, they represent completely different conditions. LN encompasses atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), which are currently considered risk factors and non-obligatory precursors of breast neoplasia. These lesions are diagnosed as incidental findings in percutaneous biopsies or appear as non-specific clusters of punctate calcifications in mammograms. ILC is the second most common breast malignancy and has typical histological features, such as infiltrative growth and low desmoplasia. These histological features are reflected in imaging findings and constitute the reasons for typical subtle mammographic features of ILC, as architectural distortion or focal asymmetries. Ultrasonography (US) may detect almost 75 % of the ILCs missed by mammography and represents the modality of choice for guiding biopsies. Magnetic resonance imaging (MRI) exhibits a high sensitivity for the diagnosis of ILC and for detecting synchronous lesions. Teaching Points • LN includes ALH and LCIS, risk factors and non-obligatory precursors of breast cancer. • Absence of e-cadherin staining is crucial for differentiation among ductal and lobular lesions. • ILC has typical histological features, such as infiltrative growth and low desmoplasia. • Mammographic features of ILC are often subtle and reflect the histological features. • MRI exhibits a high sensitivity for the diagnosis of ILC and for detecting synchronous lesions.