Psoriasis induced by first­line pembrolizumab in metastatic non­small cell lung cancer: A case report.

Therapeutic options for non-small cell lung cancer (NSCLC) have changed with the introduction of immune checkpoint inhibitors. Immunotherapy is generally well tolerated, but can also be associated with severe adverse events, such as the development of new autoimmune diseases. In patients without a history of autoimmune diseases, psoriasis caused by immunotherapy treatment is rarely described in the literature. The present study describes the case of a 68-year-old man with metastatic NSCLC that started chemoimmunotherapy with carboplatin plus pemetrexed plus pembrolizumab. After two cycles of therapy, the patient developed a G3 maculopapular rash. Biopsy confirmed psoriasis and pembrolizumab treatment was discontinued. At the last follow up, the patient was still on maintenance therapy with pemetrexed alone, which is well tolerated. Psoriasis has rarely been reported as an immune-related adverse event. Although the patient had to stop the immunotherapy treatment, the patient is still exhibiting a response to it. Notably, it has previously been described how skin toxicities are associated with a better outcome. Other studies need to be conducted to identify the risk and predictive factors associated with severe immune adverse events and objective response.

Cortical atrophy in chronic subdural hematoma from ultra-structures to physical properties.

Several theories have tried to elucidate the mechanisms behind the pathophysiology of chronic subdural hematoma (CSDH). However, this process is complex and remains mostly unknown. In this study we performed a retrospective randomised analysis comparing the cortical atrophy of 190 patients with unilateral CSDH, with 190 healthy controls. To evaluate the extent of cortical atrophy, CT scan images were utilised to develop an index that is the ratio of the maximum diameter sum of 3 cisterns divided by the maximum diameter of the skull at the temporal lobe level. Also, we reported, for the first time, the ultrastructural analyses of the CSDH using a combination of immunohistochemistry methods and transmission electron microscopy techniques. Internal validation was performed to confirm the assessment of the different degrees of cortical atrophy. Relative Cortical Atrophy Index (RCA index) refers to the sum of the maximum diameter of three cisterns (insular cistern, longitudinal cerebral fissure and cerebral sulci greatest) with the temporal bones' greatest internal distance. This index, strongly related to age in healthy controls, is positively correlated to the preoperative and post-operative maximum diameter of hematoma and the midline shift in CSDH patients. On the contrary, it negatively correlates to the Karnofsky Performance Status (KPS). The Area Under the Receiver Operating Characteristics (AUROC) showed that RCA index effectively differentiated cases from controls. Immunohistochemistry analysis showed that the newly formed CD-31 positive microvessels are higher in number than the CD34-positive microvessels in the CSDH inner membrane than in the outer membrane. Ultrastructural observations highlight the presence of a chronic inflammatory state mainly in the CSDH inner membrane. Integrating these results, we have obtained an etiopathogenetic model of CSDH. Cortical atrophy appears to be the triggering factor activating the cascade of transendothelial cellular filtration, inflammation, membrane formation and neovascularisation leading to the CSDH formation.

New Insights into Intestinal Permeability in Irritable Bowel Syndrome-Like Disorders: Histological and Ultrastructural Findings of Duodenal Biopsies.

BACKGROUND AND AIM: Diarrhea, abdominal pain, and bloating are frequent in irritable bowel syndrome (IBS)-like disorders, although little is known about their intestinal ultrastructural alterations. The aim of the present study was to study duodenal biopsies from IBS-like patients to find ultrastructural alterations. MATERIALS AND METHODS: Study design: descriptive comparative pilot study. Thirty outpatients (9 male and 21 female; median age 37.7 years; range, 20 to 65 years) complaining of IBS-like symptoms were enrolled between January 2015 to May 2019 and were divided into 6 groups, each equally consisting of 5 patients: (A) untreated celiac disease (uCD); (B) treated celiac disease (tCD); (C) wheat allergy (WA); (D) Non-celiac gluten sensitivity (NCGS); (E) Nickel allergic contact mucositis (Ni ACM); (F) controls affected by GERD. Transmission electron microscopy (TEM) morphological characteristics were: microvilli length, intermicrovillar distance, junctional complexes (JC) gap width, autophagic bodies, apoptosis, altered mitochondria, lipid/chylomicron droplets, and mast cells. Regarding JC, we focused on tight junctions (TJ), adherens junctions (AJ), and desmosomes. RESULTS: Major alterations in microvilli length and intermicrovillar distance have been observed in the subjects affected by uCD. Microvilli of tCD patients showed marked recovery after adequate GFD, although not comparable to controls. Intermediate microvillar alterations were instead observed in NCGS and Ni ACM, while characteristics of WA subjects appeared more similar to tCD. Regarding JC, TJ did not show significant differences between all groups studied, including controls. The AJ were significantly more dilated in all groups compared to controls, while no significant differences were found between the pathological groups. The distance between desmosomes was greater in uCD, NCGS, and Ni ACM than in tCD, WA, and controls. Finally, intracellular alterations have been detected in most of the groups studied although they seemed more unspecific. CONCLUSIONS: TEM analysis confirmed damages to the intestinal barrier and defense mechanisms by enterocytes in IBS-like patients, probably linked to low-grade inflammation or adverse reactions triggered by food allergens, heavy metals, or other unknown. On the other hand, our study needs confirmation and further investigations with larger populations to facilitate diagnosis, therapy, and prevention of IBS-like disorders in the future.

Malignant Insulinoma with Multiple Liver Metastases and Hypercalcitoninemia in a Patient with Type 2 Diabetes Mellitus Presenting as Recurrent Episodes of Diaphoresis due to Severe Hypoglycemia.

Insulinoma is an insulin-producing pancreatic neuroendocrine tumor that can be malignant in about 10% of cases. Locoregional invasion, lymph node metastases, or remote metastases are the main criteria of malignant insulinoma. Its incidence in patients with pre-existing diabetes mellitus (DM) is exceptionally rare. In this report, we describe a 66-year-old man with long-standing type 2 DM who presented with recurrent episodes of diaphoresis due to severe hypoglycemia despite the withdrawal of insulin therapy, hypercalcitoninemia, and biochemical and radiological findings suggestive of metastatic malignant insulinoma. Unfortunately, after few days of diazoxide treatment, edema, hypotension, oliguria, and water retention were observed, patient's clinical status deteriorated rapidly, and he died in our department from acute renal failure.

Emerging role of secreted miR-210-3p as potential biomarker for clear cell Renal Cell Carcinoma metastasis.

BACKGROUND: MicroRNAs (miRNAs) are emerging as promising molecules in the diagnosis, prognosis and treatment of urological tumours. Recently, our group performed two independent studies highlighting that miR-210-3p may be a useful biomarker not only for diagnosis but also for post-surgery clear cell Renal Cell Carcinoma (ccRCC) management. OBJECTIVE: The aim of this study is to further explore the effectiveness of miRNA as non-invasive biomarker for clinical outcomes and ccRCC response to the treatment. METHODS: We analyzed miR-210-3p levels in neoplastic and healthy tissue and in urine specimens collected at surgery and during follow-up of 21 ccRCC patients by RTqPCR. RESULTS: Firstly, we confirmed that the expression of miR-210-3p was upregulated in tumor tissues and in urine samples of analyzed cohort. Of note is that miR-210-3p expression was significantly reduced in urine samples from disease-free patients during follow-up (from 3 to 12 months) compared to the baseline levels observed at the time of surgery. In a small subgroup of patients presenting metastatic progression (such as bone, intestinal or lung metastasis), the urine levels of miR-210-3p correlated with responsiveness to the therapy. CONCLUSIONS: This pilot study highlights the relevance of secreted miR-210-3p as powerful non-invasive prognostic and predictive biomarker for the evaluation of clinical outcomes and treatment response during ccRCC follow up.

Localization of lipopolysaccharide from Escherichia Coli into human atherosclerotic plaque.

Experimental studies showed that gut-derived lipopolysaccharide (LPS) is pro-atherogenic, however, its relationship with human atherosclerosis is still to be defined. We investigate if gut-derived LPS from Escherichia Coli localizes in human carotid plaque and its potential role as pro-inflammatory molecule in the atherosclerotic lesion. LPS from Escherichia Coli and Toll-like receptor 4 (TLR4) were studied in specimens from carotid and thyroid arteries of 10 patients undergoing endarterectomy and 15 controls matched for demographic and clinical characteristics. Blood LPS were significantly higher in patients compared to controls. Immunochemistry analysis revealed positivity for antibodies against LPS and TLR4 coincidentally with positivity for CD68 only in the atherosclerotic plaque of carotid arteries but not in thyroid arteries; the positivity for LPS and TLR4 was greater in the area with activated macrophages. LPS concentration similar to that detected in atherosclerotic plaque resulted in a dose-dependent TLR4-mediated Nox2 up-regulation by human monocytes. These data provide the first evidence that LPS from Escherichia Coli localizes in human plaque and may contribute to atherosclerotic damage via TLR4-mediated oxidative stress.