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BACKGROUND: IgG4-related disease is a rare, clinical and pathologic disease entity of unknown etiology. Its main features are increased serum concentrations of IgG4 > 1,35 g/l, lymphocyte and IgG4+plasma-cell infiltration within tissues, fibrosis or sclerosis. The classical presentation of IgG4-RSD is pancreatitis which is combined with the involvement of biliary ducts in 74 percent of patients. Extrapancreatic manifestations include: abdominal or mediastinal lymphadenopathy; the involvement of salivary glands and lacrimal glands, kidneys, lung, retroperitoneum. Since IgG4-related disease is a multiorgan lymphoproliferative syndrome, it requires a careful differential diagnosis from other distinct disorders (sarcoidosis, immune rheumatic diseases, hematologic diseases, malignancies). Another distinctive feature is a fairly fast response to steroids, that represents the first-choice therapy. Immunosuppressant drugs (azathioprine, mycophenolate mofetil, methotrexate) might be chosen as glucocorticoid-sparing medications or to maintain steroid-induced remission (Fig. 1). METHODS: We report the case of a 70-year-old man and we performed a brief review of loiterature. RESULTS: Our patient has a clinical history including bronchial asthma, aortic aneurysm, histologically confirmed retroperitoneal fibrosis causing hydroureteronephrosis, prostatitis, interstitial pulmonary fibrosis, sclerosing chronic pancreatitis (histologically documented), previous chronic cholecystitis (histologically confirmed), previous pericarditis, xeroftalmia, polyclonal hypergammaglobulinemia, eosinophilia. His serum IgG4 levels were significantly increased (5560 mg/dl). In regard to the above mentioned elements a systemic disease characterized by elevated serum levels of IgG4 and IgG4-positive lymphoplasmacytic infiltrative lesions in several tissues, was suspected. Immune-rheumatic diseases and infectious diseases were excluded. Steroid treatment was started achieving a significant swift response. CONCLUSION: Until now IgG4 related disease has been considered rare in the West and exclusive of Japanese and Korean countries, our case report leads us to reflect on the necessity to take into account this disease in patients with multisystemic involvement.

Aims: We sought to compare the effects of furosemide+hypertonic saline solution (HSS) treatment in patients with acute decompensated heart failure in comparison with furosemide alone and the response in a compensated state after an acute saline load with regard to serum levels of heart failure biomarkers. Methods and results: We enrolled 141 patients with acute decompensated heart failure with reduced ejection fraction admitted to our Internal Medicine ward from March 2017 to November 2019. A total of 73 patients were randomized to treatment with i.v. high-dose furosemide plus HSS, whereas 68 patients were randomized to i.v. high-dose furosemide alone. Patients treated with furosemide plus HSS compared with controls treated with furosemide alone showed a comparable degree of reduction in the serum levels of interleukin (IL)-6, soluble suppression of tumorigenicity 2 (sST2), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the ‘between-group’ analysis. Nevertheless, patients treated with high-dose furosemide+HSS showed significantly higher absolute delta values of IL-6 (2.3±1.2 vs. 1.7±0.9, P&nbsp

Background We report an unusual case of infective colitis by Yersinia enterocolitica complicated by microliver abscesses mimicking multiple liver metastases in a 79 yr old female without any risk factors for bacteriaemia by this pathogen. Case presentation The patient was admitted to the Internal Medicine with Stroke Care ward of University Policlinico “P. Giaccone” in Palermo because of the appearance of diarrhoea. After the antimicrobial treatment for infective colitis, the clinicians observed a persistently increased white blood cells (WBC) count and multiple hepatic lesions; after having excluded any neoplastic disease and inflammatory bowel disease (IBD), blood cultures positive for Y. enterocolitica allowed to establish the final diagnosis was infective micro liver abscesses consequent to infective colitis due to Y. enterocolitica, which were successfully treated with cefixime and doxycycline. Conclusions This case report should make clinicians reflect on how complex the differential diagnosis between microliver abscesses and metastasis could be and the possibility of bacteriaemia by Y. enterocolitica even without iron overload conditions.

INTRODUCTION: Although some authors evaluated the relationship between adherence to the Mediterranean Diet (MeDi) and both ischemic and hemorrhagic stroke, hemorrhagic stroke alone is not yet examined. AIMS: We conducted a retrospective study to evaluate the relationship between adherence to MeDi and intracerebral hemorrhage (ICH) and different locations of ICH (ganglionic/internal capsule, brainstem/cerebellum, or lobar). METHODS: We analyzed charts and collected data of all consecutive patients with ICH admitted to our Internal Medicine Ward from 2005 to 2014. A scale indicating the degree of adherence to the traditional MeDi Score was constructed. RESULTS: When compared with 100 subjects without ICH, 103 subjects with ICH had significantly higher mean values of LDL (91.1 ± 38.7 mg/dl vs. 79.2 ± 34.4 mg/dl; p = 0.031), triglycerides (118.9 ± 62.9 mg/dl vs. 101.6 ± 47.6 mg/dl; p = 0.026), and proteinuria (32.6 ± 50.0 mg/dl vs. 18.1 ± 39.6 mg/dl; p=0.024) and a significantly lower mean MeDi Score (3.9 ± 1.0 vs. 7.0 ± 1.4; p < 0.0001). In a multiple regression analysis, smoking, diastolic blood pressure (DBP), and the MeDi Score remained significantly associated with ICH. We also observed a significantly lower mean MeDi Score in the lobar location group when compared with the ganglionic/internal capsule group (4.3 ± 1.0 vs. 3.5 ± 0.9; p < 0.0005). DISCUSSION: Our findings regarding the higher prevalence of ICH in patients with lower adherence to MeDi may be related to the fact that patients with lower MeDi Score exhibit a worse cardiovascular risk profile with increased risk factors such as hypertension and dyslipidemia.

Several studies suggest that inflammation has a pivotal role during the progression of osteoarthritis (OA) and cytokines have been identified as the main process mediators. This study aimed to explore the ability to modulate the main OA pro‐inflammatory biomarkers of novel gels (H‐HA/BC) based on high molecular weight hyaluronan (H‐HA) and unsulfated biotechnological chondroitin (BC). For the first time, BC was tested also in combination with H‐HA on human primary cells isolated from pathological knee joints. Specifically, the experiments were performed using an OA in vitro model based on human chondrocytes and synoviocytes. To evaluate the anti‐inflammatory effects of H‐HA/BC in comparison with H‐HA and BC single gels, NF‐kB, COMP‐2, MyD88, MMP‐13 and a wide range of cytokines, known to be specific biomarkers in OA (e.g., IL‐6, IL‐8, and TNF‐α), were evaluated. In addition, cell morphology and proliferation occurring in the presence of either H‐HA/BC or single components were assessed using time‐lapse video microscopy. It was shown that synovial fluids and cells isolated from OA suffering patients, presented a cytokine pattern respondent to an ongoing inflammation status. H‐HA and BC significantly reduced the levels of 23 biomarkers associated with cartilage damage. However, H‐HA/BC decreased significantly 24 biological mediators and downregulated 19 of them more efficiently than the single components. In synoviocytes cultures, cytokine analyses proved that H‐HA/BC gels re‐established an extracellular environment more similar to a healthy condition reducing considerably the concentration of 11 analytes. Instead, H‐HA and BC significantly modulated 7 (5 only with a longer treatment) and 8 biological cytokines, respectively. Our results suggest that H‐HA/BC beyond the viscosupplementation effect typical for HA‐based gels, can improve the inflammation status in joints and thus could be introduced as a valid protective and anti‐inflammatory intraarticular device in the field of Class III medical devices for OA treatments., Unsulfated biotechnological chondroitin by itself and complexed to hyaluronic acid counteract inflammation and improve the viability of human primary cells isolated from pathological osteoarthritis joints. Their potential efficacy, especially when combined in novel gels is supported by the modulation of several key biomarkers.

Interstitial cystitis and/or bladder pain syndrome (IC/BPS) are characterized by discomfort, abdominal pain, and pelvic pain, and they are often associated with chronic diseases. Pathological conditions related to IC/BPS can occur due to a defect in the integrity of the bladder lining. This defect has been ascribed to damage to the glycosaminoglycan (GAG) layer of the urinary epithelium. In addition, the incipient cascade of inflammation events might prompt extracellular matrix degradation. Several medical devices based on GAG instillation were proposed to re-establish epithelial integrity by GAGs binding to proteoglycans or interacting with structural urothelium. However, to date, only in vitro studies have investigated the GAG, hyaluronic acid (HA). In the present study, TNFα treatment was used to mimic IC/BPS-induced damage in bladder cells in an in vitro model. Highly purified fermentative HA and pharmaceutical grade bovine chondroitin sulfate (CSb), alone or in combination, were evaluated for the ability to counteract bladder cell damage. We evaluated NF-κB with western blots, and we analyzed interleukin 6 and 8 expression at the transcriptional and protein levels with quantitative RT-PCR, western blotting, and ELISA. We also evaluated the expression of an antibacterial peptide, human β-defensin-2. We confirmed our results in a 3D bladder epithelium model. Our results demonstrated that inflammatory status was reduced in the presence of HA, CSb, and the combination of both (HA/CSb 1.6%/2% w/v). This result suggested that these GAGs might be suitable for treating IC/BPS. All the assayed biomarkers showed that HA/CSb treatment modulated cells towards a more physiological status. Finally, we compared two commercial products suggested for the IC/BPS treatments and found that the product with more Ca++, showed enhanced anti-inflammatory activity and provided superior mucoadhesivity.

High molecular weight hyaluronan (H-HA) has a pivotal role in the maintenance of normal functions of synovial fluid and structure of the articular joint, but it has been shown that its concentration is reduced in patients affected by degenerative cartilage diseases, such as osteoarthritis (OA). The aim of this study was to investigate the anti-inflammatory effects and properties of hybrid cooperative complexes based on high and low molecular weight hyaluronan (HCC) compared to H-HA on human primary cells derived by pathological joints. In addition, the rheological behavior of HCC was evaluated in order to define their potential as viscosupplement gel in degenerated joints. The experiments were performed using an in vitro model of OA based on human chondrocytes and synoviocytes isolated from degenerated joints of patients hospitalized for surgical replacement. In order to assess the anti-inflammatory effects of HCC, we evaluated NF-kB, COMP-2, IL-6, and IL-8 as specific markers at the transcriptional and/or protein level. Moreover, the proliferative properties of HCC were assessed using time lapse video microscopy. We showed that chondrocytes and synoviocytes clearly presented an altered cytokine profile compatible with a severe ongoing inflammation status. H-HA and, above all, HCC significantly reduced levels of the specific biomarkers evaluated and improved cartilage healing. The rheological profile indicated HCC suitability for intra-articular injection in joint diseases. HCC viscoelastic properties and the protective/anti-inflammatory effect on human chondrocytes and synoviocytes suggest the novel HCC-based gels as a valid support for OA management.

Background: The crucial role of endothelium is due to the ability of endothelial cells to receive and concurrently respond to humoral and hemodynamic stimuli. The mechanisms that mediate these reactions are: the production of endothelium-derived factors and metabolizing enzymes; the expression of binding proteins and adhesive molecules; and the consequential shape changes. In fact, a wide range of anti-atherosclerotic action substances is produced by the endothelial cells with the objective of maintaining the balance between vasoconstriction and vasodilation, and inhibit or stimulate the proliferation and migration of smooth muscle cells, thrombogenesis and fibrinolysis. Smoke, age, hypercholesterolemia, hypertension, hyperglycemia, and a family history of atherosclerotic disease may induce functional and structural changes in the endothelium that imply the progressive loss of its protective role and the development of a proatherosclerotic state called endothelial dysfunction. Methods: The evaluation of the function of endothelial cells is based on the measurement of endothelial cell response to the stimulation by vasoactive substances. The endothelial response can be assessed in the coronary arteries and peripheral circulations. On our opinion, among the techniques, the most advantageous, reproducible, minimally invasive and statistically valid, as shown in many trials, is the Endo-PAT. This technique assesses endothelial function on peripheral arteries evaluating, at the level of the distal phalanx of the index finger, the vascular response to a period of ischemia in the arm induced through occlusion of the brachial artery (for five minutes) and subsequent restoration of blood flow. An additional method that is used to evaluate the state of wellness of large arteries is arterial stiffness. Arterial stiffness can be described as a reduced capability of a vessel to dilate or contract in response to pressure changes; it is defined using two parameters: compliance and distensibility. Result and Conclusion: The present review intends to clarify the mechanisms behind the development of endothelial dysfunction, and aims to show how widely proven is the correlation between endothelial dysfunction (assessed both by Endo-PAT and sphigmoCOR) and cardiovascular diseases, such as atherosclerosis, hypertension, diabetes mellitus, stroke, coronary artery disease and heart failure. Moreover, the assessment of endothelial dysfunction may represent an integral adjuvant test to identify the predisposed patients at risk for future cardiovascular accidents, as we suggest.

Background and aims Only one study has examined endothelial function in subjects with acute ischemic stroke and no study has yet assessed arterial stiffness and reactive hyperemia peripheral arterial tonometry (RH-PAT) in ischemic stroke and its clinical subtypes. Our study aimed to evaluate arterial stiffness and endothelial dysfunction indexes in patients with acute ischemic stroke and the relationship between endothelial dysfunction indexes and arterial stiffness markers and stroke subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) Classification. Methods We enrolled 98 patients with a diagnosis of acute ischemic stroke and 105 hospitalized patients without a diagnosis of acute ischemic stroke. Arterial stiffness analysis was conducted by applanation tonometry to record radial artery pressure waveform continuously; augmentation index (Aix) and pulse wave velocity (PWV) were calculated. The reactive hyperemia index (RHI) was assessed by peripheral arterial tonometry. Results In comparison to controls, ischemic stroke subjects had higher mean levels of PWV, Aix, and significantly lower mean RHI values. Compared to subjects with lacunar and cardioembolic stroke, those with Large Artery AtheroSclerosis (LAAS) subtype of stroke had higher median levels of PWV and significantly lower median levels of RHI. On multinomial logistic regression analysis of predictive variables of stroke subtype (lacunar vs. LAAS and lacunar vs. cardioembolic), we observed a negative association between RHI value and LAAS subtype and a negative association of PWV with cardioembolic subtype. Conclusions Our findings underline the relationship between endothelial and arterial stiffness index correlations in patients with acute ischemic stroke, also suggesting the use of a combination of PAT and arterial stiffness indexes to better categorize patients with ischemic stroke.

Introduction Patients with chronic liver diseases are usually thin as a result of hypermetabolism and malnutrition expressed by reduced levels of leptin and impairment of other adyponectins such as visfatin. Aims We evaluated the metabolic and inflammatory effects of intravenous high-dose furosemide plus hypertonic saline solutions (HSS) compared with repeated paracentesis and a standard oral diuretic schedule, in patients with cirrhosis and refractory ascites. Methods 59 consecutive cirrhotic patients with refractory ascites unresponsive to outpatient treatment. Enrolled subjects were randomized to treatment with intravenous infusion of furosemide (125-250mg⁄bid) plus small volumes of HSS from the first day after admission until 3 days before discharge (Group A, n:38), or repeated paracentesis from the first day after admission until 3 days before discharge (Group B, n: 21). Plasma levels of ANP, BNP, Leptin, visfatin, IL-1β, TNF-a, IL-6 were measured before and after the two type of treatment. Results Subjects in group A were observed to have a significant reduction of serum levels of TNF-α, IL-1β, IL-6, ANP, BNP, and visfatin, thus regarding primary efficacy endpoints, in Group A vs. Group B we observed higher Δ-TNF-α, Δ-IL-1β, Δ-IL-6, Δ-ANP, Δ-BNP, Δ-visfatin, Δ-Leptin at discharge. Discussion Our findings underline the possible inflammatory and metabolic effect of saline overload correction in treatment of cirrhosis complications such as refractory ascites, suggesting a possible role of inflammatory and metabolic-nutritional variables as severity markers in these patients.