The European Society of Endocrinology recommends surgical approach for suspicious adrenal mass with a limited role for adrenal biopsy. We report here a case of a patient with a 70 mm adrenal mass in whom adrenal biopsy avoided unnecessary adrenalectomy. An 80-year-old man was explored for a 67 × 41 mm suspect left adrenal tumor. Hormonal explorations were normal. 18F-FDG-PET/CT showed an increase in uptake of the adrenal mass (SUVmax: 44.6). As the diagnostic was uncertain, biopsy was performed. Pathology found T lymphocytic inflammatory infiltrate with CD4 phenotype without malignancy criteria. Simple close monitoring was decided in multidisciplinary meeting and with the patient\'s consent. At 1 and 3 months, CT and 18F-FDG-PET/CT showed a significant decrease in size and uptake of adrenal mass (40 × 20 mm and 19 × 10 mm and SUVmax 5.9 and 0.0). This report shows the interest of adrenal biopsy for well-selected cases to avoid unnecessary adrenal surgery.

To evaluate the effects of red and infrared wavelengths, separately and combined, on the inflammatory process and collagen deposition in muscle damage caused by B. leucurus venom. 112 mice were inoculated with diluted venom (0.6mg/kg) in the gastrocnemius muscle. The animals were divided into four groups: one control (CG) and three treatments, namely: 1) red laser (λ=660 nm) (RG), 2) infrared laser (λ=808 nm) (IG) and 3) red laser (λ=660 nm) + infrared (λ=808 nm) (RIG). Each group was subdivided into four subgroups, according to the duration of treatment application (applications every 24 hours over evaluation times of up to 144 hours). A diode laser was used (0.1 W, CW, 1J/point, ED: 10 J/cm2). Both wavelengths reduced the intensity of inflammation and the combination between them significantly intensified the anti-inflammatory response. Photobiomodulation also changed the type of inflammatory infiltrate observed and RIG had the highest percentage of mononuclear cells in relation to the other groups. Hemorrhage intensity was significantly lower in treated animals and RIG had the highest number of individuals in which this variable was classified as mild. As for collagen deposition, there was a significant increase in RG in relation to CG, in RIG in relation to CG and in RIG in relation to IG. Photobiomodulation proved to be effective in the treatment of inflammation and hemorrhage caused by B. leucurus venom and stimulated collagen deposition. Better results were obtained with the combined wavelengths.

Marrubiin is a diterpene with a long history of a wide range of biological activities. In this study, the anti-inflammatory effects of marrubiin were investigated using several in vitro and in vivo assays. Marrubiin inhibited carrageenan-induced peritoneal inflammation by preventing inflammatory cell infiltration and peritoneal mast cell degranulation. The anti-inflammatory activity was further demonstrated by monitoring a set of biochemical parameters, showing that the peritoneal fluid of animals treated with marrubiin had lower levels of proteins and lower myeloperoxidase activity compared with the fluid of animals that were not treated. Marrubiin exerted the most pronounced cytotoxic activity towards peripheral mononuclear cells, being the main contributors to peritoneal inflammation. Additionally, a moderate lipoxygenase inhibition activity of marrubiin was observed.

BACKGROUND: Nasal polyps (NPs) represent the end-stage manifestation of chronic rhinosinusitis (CRS), a relatively common pathological condition encountered in all ages of life.
METHODS: The aim of our study was to evaluate the histological features and inflammatory cellular components of NPs in a retrospective cohort (143 cases) of pediatric, adult and elderly populations in order to discuss the possible morphological age-related differences statistically documented.
RESULTS: In the pediatric group, the inflammatory infiltrate presented many eosinophils mixed with lymphocytes, while in the adult population, lymphocytes and plasma cells were mainly evident, frequently with a perivascular distribution or with the formation of subepithelial lymphoid nodules. In the elderly population, inflammation was less evident and was associated with cavernous-like angecthatic structures with thrombotic stratification. Nearly all morphological findings exhibited statistically significant values among differently aged subgroups.
CONCLUSIONS: Our results support the presence of histological specificities of NPs at different ages of life, providing new insight into the etiopathogenesis of NPs. The future role of biological therapies, mainly in cases refractory to already available standard medical and surgical treatments, may be analyzed by a prospective study using a larger cohort with a long-term evaluation also in relation to a possible relapse.

Autoimmune hepatitis (AIH) is a necroinflammatory disease that occurs when genetically susceptible individuals are exposed to an environmental trigger. It is a rare disease, and its epidemiological aspects are nearly unknown in Northeast Brazil. In the literature, the activation of components of the inflammatory cascade pathways, including interleukins such as TNF-α and signaling factors like MAPK-p38 and NFκB, in the pathogenesis of AIH is well described in animal models. This study evaluated, for the first time, the immunostaining of TNF-α, MAPK-p38, and NFκB in immunohistochemical analysis of liver biopsies from AIH patients. The activation of the MAPK-p38 pathway was also studied through immunoassay analysis in the peripheral blood of AIH patients.
Data from medical records of 25 AIH patients were analyzed. Histological and immunohistochemical analysis of liver tissue obtained from biopsies was performed to detect NFκB, MAPK-p38, and TNF-α. Immunoassay analysis of the MAPK-p38 pathway was performed in peripheral blood from 18 AIH patients and 8 healthy volunteers. Medical record analysis showed an average age of 33.3 years, with a female predominance in a ratio of 7.3:1. Concomitance with other autoimmune diseases was observed in 36 % of patients, with thyroid disorders being the most prominent among them, and an 8 % indication for liver transplantation. In the evaluation of autoantibodies, ANA was detected in 52 %, followed by SMA at 20 %, and Anti-LKM-1 at 16 %. Liver biopsy findings were like the global literature, with interface hepatitis and lymphoplasmacytic infiltration observed. Immunohistochemical analysis showed immunostaining for NFκB, MAPK-p38, and TNF-α, corroborating the inflammatory and immunological characteristics of the disease. Immunoassay analysis in peripheral blood confirmed the activation of the MAPK-p38 signaling pathway, with a statistically significant difference between AIH patients and healthy controls.
The epidemiological and histological findings of AIH in this study in Northeast Brazil were like global population data. Immunohistochemical analysis of liver tissue and immunoassay analysis in peripheral blood confirmed the activation of TNF-α and the NFκB and MAPK-p38 signaling pathways in AIH patients.

Rectal cancer constitutes over one-third of all colorectal cancers (CRCs) and is one of the leading causes of cancer-related deaths in developed countries. In order to identify high-risk patients and better adjust therapies, new markers are needed. Systemic inflammatory response (SIR) markers such as LMR, NLR, and PLR have proven to be highly prognostic in many malignancies, including CRC; however, their roles in locally advanced rectal cancer (LARC) are conflicting and lack proper validation. Sixty well-selected patients with LARC treated at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, between August 2017 and December 2020 were prospectively enrolled in this study. The reproducibility of the pre-treatment levels of the SIR markers, their correlations with clinicopathological characteristics, and their prognostic value were evaluated. There was a significant positive correlation between LMR and cancer-related inflammatory infiltrate (r = 0.38, p = 0.044) and PD-L1 expression in tumor cells, lymphocytes, and macrophages (combined positive score (CPS)) (r = 0.45, p = 0.016). The PLR level was correlated with nodal involvement (p = 0.033). The SIR markers proved to be only moderately reproducible and had no significant prognostic value. In conclusion, the LMR was associated with local cancer-related inflammation and PD-L1 expression in tumor microenvironments. The validity of SIR indices as biomarkers in LARC requires further investigation.

BACKGROUND: Extracellular matrix (ECM) suffers substantial alterations after myocardial infarction (MI), including the invasion of leukocyte subtypes. Despite a complete reopening at epicardial level, hypoperfusion within the infarcted myocardium, known as microvascular obstruction (MVO), occurs and exerts a negative impact on ventricular remodeling. In this study, ECM composition at MVO regions was described using a morphometric analysis.
METHODS: MI was induced in female swine (n = 10) by transitory 90-minute coronary occlusion followed by seven days of reperfusion. Prior to euthanasia, intracoronary thioflavin-S was infused. Within the infarcted myocardium, regions displaying MVO (thioflavin-S-) or no MVO (thioflavin-S+) were isolated and stained to morphometrically compare ECM composition.
RESULTS: As reflected by cell invasion through ECM, areas with MVO displayed an enlarged presence of neutrophils and lymphocytes, whilst no differences in the amount of macrophages and myofibroblasts were detected compared to infarcted myocardium without MVO. Indeed, those regions with macroscopic MVO showed lower capillary density than areas without MVO. Lastly, a significant reduction in the extension of total collagen, type I, but not type III, collagen, laminin, and fibronectin together with an augmentation of polysaccharides were noted in areas showing MVO compared to those without microvascular injury.
CONCLUSIONS: ECM composition in infarcted regions with MVO isolated from female swine displays a higher presence of inflammatory infiltrate and polysaccharides as well as reduced number of microvessels and collagen content compared to those areas without microvascular hypoperfusion. These characteristics might underlie the development of adverse ventricular remodeling in MI patients with extensive MVO.

OBJECTIVE: This study aimed to evaluate the influence of high-fat diet (HFD) and melatonin (MEL) treatment on the progression of inflammation and alveolar bone resorption (ABR) in rats with AP.
METHODS: Forty male Wistar rats were divided into four groups: apical periodontitis (AP), HFDAP, APMEL and HFDAPMEL. The animals were fed an HFD or standard diet for 107 days. On the 7th day, the rats were subjected to AP, and after 70 days, the rats in the MEL groups were treated with MEL for 30 days. Post treatment, the animals were euthanized, and their jaws were retrieved for evaluation of bone resorption, intensity of the inflammatory response, and immunohistochemical analysis including tartrate-resistant acid phosphatase (TRAP) and interleukin-1β (IL-1β) levels and tumor necrosis factor (TNF)-α expression.
RESULTS: The APMEL group showed reduction in the inflammatory infiltrate and IL-1β expression relation to HFDAP, while the TNF-α levels did not differ among the groups. The HFDAP group showed an increase in the ABR. MEL reduced the TRAP levels in the APMEL and HFDAPMEL groups.
CONCLUSIONS: while MEL could reduce TRAP levels in the APMEL and HFDAPMEL groups, the reduction in the HFDAPMEL group was smaller than that in the APMEL group, demonstrating that the interaction between AP and HFD decreased the anti-resorptive effects of MEL.

Pathological and inflammatory events in muscle after the injection of snake venoms vary in different regions of the affected tissue and at different time intervals. In order to study such heterogeneity in the immune cell microenvironment, a murine model of muscle necrosis based on the injection of the venom of Daboia russelii was used. Histological and immunohistochemical methods were utilized to identify areas in muscle tissue with a different extent of muscle cell damage, based on the presence of hypercontracted muscle cells, a landmark of necrosis, and on the immunostaining for desmin. A gradient of inflammatory cells (neutrophils and macrophages) was observed from heavily necrotic areas to less damaged and non-necrotic areas. GeoMx® Digital Spatial Profiler (NanoString, Seattle, WA, USA) was used for assessing the presence of markers of various immune cells by comparing high-desmin (nondamaged) and low-desmin (damaged) regions of muscle. Markers of monocytes, macrophages, M2 macrophages, dendritic cells, neutrophils, leukocyte adhesion and migration markers, and hematopoietic precursor cells showed higher levels in low-desmin regions, especially in samples collected 24 hr after venom injection, whereas several markers of lymphocytes did not. Moreover, apoptosis (BAD) and extracellular matrix (fibronectin) markers were also increased in low-desmin regions. Our findings reveal a hitherto-unknown picture of immune cell microheterogeneity in venom-injected muscle which greatly depends on the extent of muscle cell damage and the time lapse after venom injection.

Non-melanoma skin cancer (NMSC) is the most common type of neoplasm affecting Caucasian individuals, with squamous-cell carcinoma (cSCC) being the second most common type of NMSC after basal-cell carcinoma. The immunohistochemical study of cSCC is of particular importance, especially for the diagnosis of its rare forms, for which accurate and early diagnosis is crucial for survival. In the present review of the literature, the potentially significant value of immunohistochemical markers were highlighted to more accurately assess the biological behaviour, the prognosis of cSCC and to optimize case management. The immunohistochemical markers were classified from a pathophysiological point of view in order to present the mechanism by which carcinogenesis occurs with its subsequent evolution and therefore, to develop a more accurate novel risk staging criteria for this type of neoplasm.