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P2X7R-NLRP3 and AIM2 inflammasomes activate caspase-1 and the release of cytokines involved in viral-related liver disease. Little is known about their role in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). We characterized the role of inflammasomes in NAFLD, NASH, and HCV. Gene expression and subcellular localization of P2X7R/P2X4R-NLRP3 and AIM2 inflammasome components were examined in histopathological preparations of 46 patients with biopsy-proven viral and metabolic liver disease using real-time PCR and immunofluorescence. P2X7R, P2X4R, and Caspase-1 are two- to five-fold more expressed in patients with NAFLD/NASH associated with chronic HCV infection than those with metabolic damage only (p ≤ 0.01 for all comparisons). The AIM2 inflammasome is 4.4 times more expressed in patients with chronic HCV infection, regardless of coexistent metabolic abnormalities (p = 0.0006). IL-2, a cytokine playing a pivotal role during chronic HCV infection, showed a similar expression in HCV and NASH patients (p = 0.77) but was virtually absent in NAFLD. The P2X7R-NLRP3 complex prevailed in infiltrating macrophages, while AIM2 was localized in Kupffer cells. Caspase-1 expression correlated with elastography-based liver fibrosis (r = 0.35, p = 0.02), whereas P2X7R, P2X4R, NRLP3, Caspase-1, and IL-2 expression correlated with circulating markers of disease severity. P2X7R and P2X4R play a major role in liver inflammation accompanying chronic HCV infection, especially when combined with metabolic damage, while AIM2 is specifically expressed in chronic viral hepatitis. We describe for the first time the hepatic expression of IL-2 in NASH, so far considered a peculiarity of HCV-related liver damage. [ABSTRACT FROM AUTHOR]

Purpose: Functional and aesthetic results after septorhinoplasty (SRP) are often not clearly demonstrated. There is still an open topic in the literature about analysis of aesthetic, functional results and patients' satisfaction after SRP. The aim of our study is to determine patients' satisfaction after SRP and concomitant radiofrequency of the inferior turbinate (RF) regarding nose appearance and improvement of symptoms, using patient reported outcome measures (PROMs). Methods: ROE questionnaire and the NOSE scale were used for a retrospective evaluation to assess patient's satisfaction in 369 patients undergoing SRP surgery from 2003 to 2016. Two additional questions were asked to confirm satisfaction following surgery. Results: 258 patients completed the questionnaires (71.7%). The global average ROE score was 18.14 (75.6%). The percentage of satisfaction of aesthetic result was 87.3%, in particular 10.5% were very happy, 57% very much satisfied and 19.8% moderately satisfied. The global post-operative average NOSE score was 13.1 with the resolution of nasal obstruction in 72.1% cases and a marked improvement in 9.3%. The results of the two additional questions showed that 81% of patients would undergo the procedure again if required and 72.1% of patients were globally satisfied. Conclusions: Our study demonstrates the utility of PROMs in evaluating aesthetic and functional results after SRP and simultaneous RF. In our series, the patients undergoing SRP and RF are generally satisfied by the functional and aesthetic results. This kind of assessments should be the most common post-operative evaluation methods in this surgery. [ABSTRACT FROM AUTHOR]

Open surgery is a reliable choice for congenital subglottic stenosis, that represents the third most common congenital anomaly of the larynx. One of the procedures performed is anterior laryngotracheal reconstruction (LTR) with anterior rib graft. The objective of this preliminary study was to evaluate the potential of 3D printing technology for the realization of laryngo-tracheal scaffold in Polycaprolactone (PCL) implanted in vivo in ovine animal model. A 3D computer model of a laryngeal graft and a tracheal graft was designed and printed with PCL through 3D additive manufacturing technology. The scaffolds were seeded with autologous mesenchymal stem cells and cultured in vitro for up to 14 days. Anterior graft LTR with 3D printed scaffolds was performed on 5 sheep. The animals underwent endoscopic examinations at the first, 3rd, 6th, and 12th weeks after surgery and before sacrifice. The integration of the material was evaluated by the pathologist. Two animals showed a favourable postoperative course and were sacrificed at 6 months postoperatively. In these cases, we observed endoscopically a complete integration of the cellularized PCL scaffold into the peri-implant tissues, and the pathologist found the growth of respiratory epithelium on the scaffold's inner surface. Other two animals showed a difficult post-operative recovery characterized by respiratory distress resulting in early sacrifice on postoperative days 31 and 33. In these animals we found a poor integration of the grafts into the tracheal structure, and a better integration of the laryngeal scaffold. The last animal developed a wound abscess and was sacrificed 80 days after surgery. We observed, in this case, a poor scaffold integration and an acute inflammatory reaction. From the preliminary data obtained we found that the excessive stiffness of the material, along with the anatomical features of the sheep, is a major limitation of this study. It will be necessary in the future to create a new biocompatible, more flexible and elastic graft, to achieve greater integration into surrounding tissues. Bioconstructed grafts could simplify surgery for the treatment of laryngo-tracheal stenosis, particularly in the treatment of long tracheal stenoses, which have, at the moment, very complex surgical options. NA. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) displays a worse prognosis in subjects with type 2 diabetes (T2D); effective treatments are, so far, scanty. Semaglutide showed efficacy in improving steatohepatitis. We longitudinally observed a MASLD cohort of T2D subjects starting semaglutide, to detect an improvement of non-invasive surrogates of steatosis and fibro-inflammatory liver involvement, evaluating the role of mild alcohol consumption. Patients and methods: In 62 overweight/obese T2D subjects with MASLD (36 non-drinker and 26 mild alcohol consumers), anthropometric, bio-humoral and transient elastography (TE) data were collected before (T0) and after an average time of 6.4 month (T1) from injective semaglutide prescription. Circulating levels of hormones (GIP, GLP-1, glucagon, insulin) and inflammatory markers (TNFα, MCP-1, IL-18, IL-10) were measured. Steatotic and necro-inflammatory liver involvement was evaluated with FibroScan controlled attenuation parameter (CAP) and liver stiffness (LS), respectively. Results: Significant (p < 0.006) T0-T1 reductions of BMI, waist circumference, fasting glucose, and HbA1c were observed. AST (-10 ± 3 IU/L), ALT (-18 ± 5 IU/L), GGT (-33 ± 15 IU/L), CAP (-25 ± 8 dB/m) and LS (-0.8 ± 0.4 kPa) were reduced, too. GLP-1 increased (+ 95.9 pM, p < 0.0001) and IL-18 was reduced (-46.6 pg/ml, p = 0.0002). After adjustment for confounders, CAP improving was only related to GLP-1 increase (ß=-0.437, p = 0.0122). Mild alcohol intake did not influence these relations. Conclusion: Use of semaglutide in subjects with T2D and MASLD is associated with a significant decline of liver steatosis and necroinflammation proxies; mild alcohol assumption did not exert any influence. An independent effect of GLP-1 raise was observed on reduction of steatosis, irrespective of alcohol consumption. [ABSTRACT FROM AUTHOR]

Purpose: Inhalation of a foreign body is a real emergency in pediatric age and requires prompt diagnosis and treatment to reduce mortality. The objective of this study is to analyze clinical and radiological details, types, and localization of foreign bodies in patients conducted or to our hospital with suspected inhalation. Methods: We conducted a retrospective analysis of all cases of foreign body inhalation admitted to our Pediatric Emergency Room between January 2009 and June 2022. Results: 171 patients were included in the study. In 83 patients, the FB was detected. The mean age of presentation was 2.3 years (SD: ± 2). Cough (73%) and unilateral reduced breath sound (51%) were the most common clinical symptom and clinical sign. The most frequent localization was the right main bronchus (43%). The foreign bodies retrieved were vegetable (83%), of which peanut was the most common. Chest radiographs were normal in 25%. The mean duration of hospitalization was 5 days (± 2.9). Complications such as pneumothorax were seen in two cases. Conclusions: Foreign body inhalation represents a true pediatric emergency and still a challenge in clinical practice. The best way to manage it is an early diagnosis and removal by fully trained staff. [ABSTRACT FROM AUTHOR]

[Display omitted] • Functional ice cream is healthy and helps reduce the risk of diseases. • The most important functionalization is the replacement of fats and sugars. • Partial replacement of fat should not alter texture and flavour release. • Functional ice cream is an excellent carrier of bioactive ingredients. • Health ingredients are bioactive compounds, antioxidants, vitamins, minerals, fibre. The increased interest in foods which improve human health and nutrition has led to the need for academia and food industry to invest in the development of innovative and functional ice cream. Since ice cream is the most popular frozen dairy product, it shows good potential to help people improve their diets by reducing the intake of certain nutrients associated with the increased risk of obesity and other related diseases. Moreover, it supplies beneficial and essential components. However, the reduction or removal of common ice cream ingredients or the addition of uncommon ingredients to the standard formulation must not spoil the sensory characteristics and storage stability of ice cream. Hence, to keep the appeal of ice cream high, the food industry is subjected to constant challenges, since functional ice cream must be tasty as well as beneficial. The review focuses on the healthy aspects and sensory implications of ice cream functionalization. In the first part, different replacing strategies such as the substitution of fat and sugar are discussed. In the second part, ice cream enriched with functional ingredients is debated. [ABSTRACT FROM AUTHOR]

Background: Although liver biopsy remains the gold standard for the diagnosis and the monitoring of liver disease, non-invasive biomarkers have been recently suggested to predict liver disease severity, progression, and response to therapy. We investigated multiple tissue and circulating markers of angiogenesis in predicting the severity of biopsy-validated chronic liver diseases in patients with chronic hepatitis C virus (HCV) and in NAFLD/NASH patients. Methods: We studied samples from forty-six patients with HCV and/or NAFLD who underwent liver biopsy, liver ultrasonography, and liver stiffness measurement. Ishak and Brunt scores were calculated. Expression of selective genes and luminex analyses of 17 different circulating pro-angiogenic factors were performed. Results: The phenotype of NAFLD/NASH or HCV subjects was similar, except for insulin, which was expressed at higher levels in NAFLD/NASH patients. A Mann–Whitney test showed significant differences for the circulating levels of HB-EGF and for follistatin between HCV and NAFLD/NASH patients. In HCV patients, we found an inverse correlation between disease stage and BMP-9 and VEGF-A circulating levels, while in NASH/NAFLD direct correlations between stage and BMP-9 and VEGF-A circulating levels were noted. The K-means algorithm divided HCV and NASH/NAFLD patients in two clusters with significant differences between them. Logistic regression models showed a positive relationship with BMP-9 levels for NASH/NAFLD and with HB-EGF circulating concentrations for HCV. ROC analysis showed for BMP-9 > 1188 pg/mL a worse disease in NASH/NAFLD, whereas for HB-EGF < 61 pg/mL a higher severity of disease in HCV. Conclusion: Our data show that circulating biomarker profiles can identify the severity of chronic liver disease of NAFLD/NASH or HCV origin. [ABSTRACT FROM AUTHOR]

Surgery, external beam radiotherapy (EBRT), and interventional radiotherapy (IRT, BrachyTherapy BT) are the current therapeutic options for nose vestibule (NV) squamous cell carcinoma (SCC). In this article, we evaluate the nose functional parameters of patients affected by SCCs of the NV, primarily treated by interstitial IRT comparing them with healthy controls and with patients treated with intensity-modulated EBRT. Ten patients treated by using IRT (group 1), 10 healthy controls and eight patients treated by EBRT (group 2) on the region of the nose were submitted to clinical evaluation (with the NOSE scale score), rhinomanometry, olfactory testing, nasal citology, and evaluation of mucociliary clearance through saccharine test. No long-term skin or cartilaginous toxicity are recorded. The olfactometry threshold discrimination identification TDI is lower in EB group. The mean NOSE scale score was significantly higher in group 2 than in group 1 and healthy controls (p < 0.05). The distribution of cytologic patterns resulted significantly different as well. Patients treated by EB have a significantly impaired mucociliary clearance, with a mean time for the transport of the stained marker, which is more than double in the patients treated by EB than in those treated with IRT (p < 0.001). Nasal function and cytological findings are significantly better, substantially preserved, in patients treated by IRT than in those treated by EBRT, bringing new relevant evidence for the establishment of interstitial IRT as the new standard for the treatment of the primary lesion in cT1 and cT2 -Wang staging NV SCCs. [ABSTRACT FROM AUTHOR]

Summary: Background: Virus, host factors and their interplay influence Hepatitis B surface Antigen serum levels during Hepatitis B Virus (HBV) infection course and treatment. Aim: To study the Pre‐S/S circulating quasispecies in a cohort of untreated, HBeAg negative, genotype‐D, HBsAg carriers. Methods: We studied 260 carriers: 71 with HBeAg negative infection (ENI; HBV‐DNA ≤2000 IU/mL); 42 Grey Zone (GZ; HBV‐DNA ≤20 000 IU/mL); 82 chronic hepatitis (CH) and 65 cirrhosis (CI) (HBV‐DNA > 20 000 IU/mL). Population sequencing was applied to identify Pre‐S/S gene mutations responsible for any amino acid substitution or potential biological/antigenic implications (M‐muts) on HBsAg. Results: HBsAg serum levels were lower in ENI + GZ than in CH + CI (2.61 [−1.10/4.06] vs 3.62 [2.41/4.92] log10IU/mL, P < 0.001) and in CI than CH (3.48 [2.41/4.38] vs 3.66 [2.57/4.92] log10 IU/mL, P < 0.001). M‐muts were found in 73 (28.1%) cases: 5 (7.0%) ENI, 3 (7.1%) GZ, 26 (31.7%) CH, 39 (60.0%) CI (P < 0.001) and mostly in Pre‐S2 (17.6%) than Pre‐S1 (5.8%) and Small‐S (10.8%; P < 0.001). Overall HBsAg serum levels were higher in carriers with M‐muts (3.56 [0.95/4.38] vs 3.17 [−1.10/4.92] log10 IU/mL, P < 0.001), but comparable in carriers with or without M‐mut when considering separately ENI + GZ (2.84 [0.95/3.89] vs 2.61 [−1.10/4.06] log10IU/mL, P = 0.330] and CH + CI (3.57 [2.67/4.38] vs 3.63 [2.41/4.92] log10IU/mL, P = 0.37). Infection phase (β: 0.422, P < 0.001), age (β: −0.260, P < 0.001), ALT (β: −0.103, P = 0.045), liver stiffness (β: −0.118, P = 0.039) and HBV‐DNA (β: 0.384, P < 0.001), but not M‐mut were independently associated with HBsAg serum levels. Conclusions: In HBeAg negative, genotype‐D, carriers Pre‐S/S heterogeneity increases with severity of liver disease, but does not influence HBsAg serum levels, that in low viraemic carriers are associated with an effective control of HBV. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease is becoming a global epidemic. The aim of this study was to develop a system for assessing liver fat content based on ultrasound images. Magnetic resonance spectroscopy measurements were obtained in 61 patients and the controlled attenuation parameter in 54. Ultrasound images were acquired for all 115 participants and used to calculate the hepatic/renal ratio, hepatic/portal vein ratio, attenuation rate, diaphragm visualization and portal vein wall visualization. The Steato-score was obtained by combining these five parameters. Magnetic resonance spectroscopy measurements were significantly correlated with hepatic/renal ratio, hepatic/portal vein ratio, attenuation rate, diaphragm visualization and portal vein wall visualization; Steato-score was dependent on hepatic/renal ratio, attenuation rate and diaphragm visualization. Area under the receiver operating characteristic curve was equal to 0.98, with 89% sensitivity and 94% specificity. Controlled attenuation parameter values were significantly correlated with hepatic/renal ratio, attenuation rate, diaphragm visualization and Steato-score; the area under the curve was 0.79. This system could be a valid alternative as a non-invasive, simple and inexpensive assessment of intrahepatic fat. [ABSTRACT FROM AUTHOR]

Background & Aims The difference between the long-term outcome of low-viraemic ( HBV- DNA≤20 000- IU/ mL, LV- AC) and inactive HBsAg carriers ( HBV- DNA≤2000- IU/ mL, IC) remains to be defined. We studied prospectively 153 HBeAg-negative HBsAg-carriers with baseline HBV- DNA≤20 000- IU/ mL and normal transaminases. Methods IC, LV- AC or chronic hepatitis B ( CHB) ( HBV- DNA persistently ≤2000- IU/ mL, ≤20 000- IU/ mL or >20 000- IU/ mL respectively) were diagnosed after 1-year, 3-monthly monitoring. Thereafter IC and LV- AC were followed-up for additional 57.2 (8.5-158.3) months. HBV- DNA, HBsAg, HBV'core-related'Antigen ( HBcrAg) and total-anti- HBc were quantified at baseline. Results After the 1st year diagnostic follow-up CHB [higher HBV- DNA ( P=.005), total-anti- HBc ( P=.012), ALT ( P=.007) and liver-stiffness ( P=.021)] was identified in 20 (13.1%) carriers; baseline HBsAg≤1000 IU/ HBV- DNA≤2000 IU/ mL excluded the presence of CHB ( NPV-100%). Thereafter, during the long-term follow-up none of 87 IC reactivated, 19 (21.8%) cleared HBsAg [older-age ( P=.004), lower HBsAg ( P<.001), higher yearly HBsAg decline ( P<.001)]. Twenty-five of 46 (54.3%) LV- AC remained stable, 20 (43.5%) became IC and 1 (2.2%) developed CHB. The best single-point CHB and IC diagnostic-accuracies were total-anti- HBc (84.2%, NPV-98.2%) and HBV- DNA/total-anti- HBc/ HBcrAg combination (89.5%, 93%-sensitivity, 84.8%-specificity) respectively. Conclusions Viraemia persistently ≤20 000- IU/ mL predicts a benign clinical outcome: it was associated with transition to IC in 43% of LV- AC and to Occult HBV Infection in 20% of IC within 5-years. Nevertheless, 13.1% of individuals with low viraemia at presentation develops CHB within 1 year: 1-year HBV- DNA monitoring resulted the most accurate diagnostic approach that can be limited to at least a half of cases by the single point HBV- DNA/ HBsAg quantification. The IC-diagnostic-accuracy combining HBV- DNA/total-anti- HBc/ HBcrAg needs to be confirmed in further studies. [ABSTRACT FROM AUTHOR]

Aims: Obesity-induced nephropathy is an established clinical entity arising from a 'maladaptive' response to lipid accumulation at the nephron level. Bariatric surgery positively affects renal function, reducing or increasing glomerular filtration rate (GFR) in subjects with hyperfiltration and renal impairment, respectively. The effect of this surgery in patients with normal estimated GFR (eGFR) is less clear. Methods: A complete clinical and biochemical assessment of 135 severely obese, otherwise healthy subjects, was obtained before Roux-en-Y gastric bypass (RYGB). All subjects underwent an OGTT with plasma glucose and insulin determinations. Follow-up data were recorded at 6, 12, 24 and 48 months after intervention. Results: Baseline eGFR was 98.2 ± 13.6 ml/min/1.73 m; hyperfiltration (>120 ml/min/1.73 m) was present in 7% of the cohort. No eGFR variation over the follow-up emerged, except at the last visit (−3.6 ± 1.4 ml/min/1.73 m at month 48, p = 0.01 vs baseline). In the univariate analysis, the renal performance at 48 months was inversely related to baseline eGFR ( r = −0.17, p = 0.04) and plasma triglycerides ( r = −0.04, p = 0.05). Fasting and OGTT-derived variables did not impact eGFR. By multiple regression analysis, eGFR time course was independently predicted only by baseline eGFR ( p = 0.03). Interestingly, patients having a baseline eGFR >100 ml/min/1.73 m (median value) showed, after 48 months, an average loss of −8.3 ± 2.2 ml/min/1.73 m, while those with eGFR <100 exhibited a slight increase (+1.8 ± 2.3 ml/min/1.73 m, p < 0.01). Conclusions: Long-term data confirm the safety of RYGB on renal function. Interestingly, a subtle hyperfiltration, i.e., occurring in high-normal range of eGFR, is attenuated by surgical procedure. Lastly, high serum triglycerides may track an unfavorable renal outcome. [ABSTRACT FROM AUTHOR]

The role of elective neck dissection during salvage surgery in patients with a clinically negative neck (cN0) is still discussed. The main objective of this work was to estimate the prevalence and predictive factors of occult neck nodes metastasis; we therefore aimed to evaluate the survival rate and the main oncologic outcomes of cN0 patients who underwent salvage total laryngectomy and elective bilateral neck dissection. In this retrospective observational study, we enrolled 80 cN0 patients affected by recurrent laryngeal cancer and who underwent salvage total laryngectomy and bilateral selective elective neck dissection. Several parameters were collected in order to find prognostic factors; finally, postoperative complications were reviewed and survival analysis was performed. Occult lymph node metastases were reported in 18 out of 80 patients (22.5%). Significant statistical correlation between lymphovascular invasion (p = 0.007), perineural invasion (p = 0.025) and occult nodal metastasis was found. Other variables (glottic subsite of recurrence, clinical T, pathological T, previous chemotherapy) were not significantly predictive of occult nodal metastasis. The 5-year OS, DSS, and RFS were 50.4%, 64.7%, and 63.4%, respectively. In conclusion, our single-institution data on a large cohort of patients, suggest performing routinely elective selective bilateral neck dissection during salvage total laryngectomy in cN0 patients due to the biological attitude of the tumor to spread to cervical nodes, considering an acceptable complications rate. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) may induce hepatitis B virus (HBV) reactivations in co-infected patients, whose dynamics and outcomes could depend on the phase of HBV infection. We investigated HBsAg and HBV-DNA kinetics in fifteen untreated HBeAg Negative Infection (ENI) (4F-11M, 62.1y) and eight Nucleos(t)ide Analogs (NAs) treated Chronic Hepatitis B (CHB) (3F-6M, 54.8y) with HCV co-infection, receiving DAAs-regimens including Sofosbuvir (13) or not (10). All achieved a sustained virologic response (SVR) and normalized alanine-aminotransferase (ALT). At the direct acting antivirals' (DAAs) baseline (BL), the HBV-DNA was undetectable (<6 IU/mL) in eight ENI and all CHB, the mean Log-HBsAg was lower in ENI than CHB (0.88 vs. 2.42, p = 0.035). During DAAs, HBV-DNA increased in untreated ENI by >1 Log in five and became detectable in two. Accordingly, mean BL Log-HBV-DNA (0.89) increased at week-4 (1.78; p = 0.100) and at the end of therapy (1.57; p = 0.104). Mean Log-HBsAg decreased at week-4 in ENI (from 0.88 to 0.55; p = 0.020) and CHB (from 2.42 to 2.15; p = 0.015). After DAAs, the HBsAg returned to pre-treatment levels in CHB, but not in ENI (six cleared HBsAg). Female gender and SOF were associated with a greater HBsAg decline. In conclusion, HBV reactivations during DAAs in HCV co-infected ENI caused moderate increases of HBV-DNA without ALT elevations. The concomitant HBsAg decline, although significant, did not modify individual pre-treatment profiles. [ABSTRACT FROM AUTHOR]

Objective Smoking is a recognized cardiovascular risk factor. Perivascular visceral adipose tissue ( PVAT) is a source of inflammatory molecules, thus contributing to atherosclerosis progression. The P2 X7 receptor ( P2 X7 R)-inflammasome complex, crucial in determining IL-1β and IL-18 release, participates in this scenario. We evaluated whether smoking might affect the PVAT inflammatory phenotype and explored the putative role of the axis P2 X7 R-inflammasome in this picture. Subjects and Methods TNFα, IL-6, RBP4, MCP-1, as well as P2 X7 R and inflammasome components NLRP3, ASC, caspase-1 and IL-1β and IL-18 expression was determined in adipocytes isolated by PVAT of healthy smokers ( Smok) and nonsmokers ( No- Smok) subjects. Plasma and culture medium levels of these cytokines were also determined. Results Perivascular adipose tissue of Smok had a higher expression of P2 X7 R and inflammasome components; via P2 X7 R activation, it released more IL-1β and IL-18, whose serum levels were also higher in Smok than in No- Smok. Linear correlations of NLRP3 with P2 X7 R and IL-18 expression and release emerged. Smok also had a higher PVAT expression of the chemotactic factor MCP-1. However, no difference was observed in the PVAT expression of genes more strictly related to insulin resistance, like TNFα, RBP4, IL-6; this was coupled with similar plasma levels of TNFα and RBP4 in the two groups. Conclusion Smoking contributes to the pro-inflammatory status of the PVAT by enhancing expression and activity of the P2 X7 R-inflammasome complex; the effect on adipocytokines more related to insulin resistance and metabolic abnormalities appears trivial. [ABSTRACT FROM AUTHOR]

Abstract: Objective: P2X7 receptor (P2X7R), upon its stimulation with extracellular ATP, modulates several inflammatory responses in different cell types. No information is available on its presence in human adipocytes and its potential involvement in the chronic inflammation associated with metabolic syndrome (MS). Therefore, we evaluated P2X7R presence and functional activity in adipocytes from visceral (VAT) and subcutaneous (SAT) adipose tissue of patients with MS and controls (CTL). Methods: Adipocyte gene expression of TNFα, IL-6 and PAI-1 (by realtime-PCR) and their plasma concentrations (ELISA); P2X7R expression (realtime-PCR, Western blot and immunofluorescence); P2X7R functional activity (intracellular calcium fluxes by fluorimetry); cytokine release from adipocytes (ELISA). The inflammasome components were also determined. Results: In VAT, TNFα, IL-6 and PAI-1 were more expressed in MS than in CTL. These differences were confirmed in SAT for IL-6 and PAI-1. Plasma IL-6, PAI-1 and TNFα levels were higher in MS. P2X7R mRNA and protein, identified in both VAT and SAT, were more abundant in MS than in CTL. Immunofluoresce confirmed the typical “ring-like” arrangement of P2X7R at the plasma membrane. Benzoyl-benzoyl-ATP raised intracellular calcium both in VAT and SAT, and induced IL-6, TNFα and PAI-1 release in both MS and CTL cells. This effect was partially inhibited by KN62, specific human P2X7R blocker, or by P2X7R gene silencing. The inflammasome was more activated in MS than in CTL adipocytes. Conclusion: Human adipocytes express functionally active P2X7R, which modulate the release of inflammatory cytokines, at least in part via inflammasome activation. Adipocytes from MS patients show an enhanced P2X7R expression, which might contribute to the subclinical inflammatory status characterizing these patients and conferring them an increased CV risk. [Copyright &y& Elsevier]

Simple Summary: Systemic therapy in advanced hepatocellular-carcinomas (HCC) has limited benefits, but some patients show partial responses (PR) and a few even a complete response (CR). Understanding the biological mechanisms could help clinicians in decision-making. Aim of this study was to develop a physic-mathematical model to investigate tumor dynamics using α-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-II) measures combined with digital imaging. The model was set-up in three prototype patients with CR/PR to sorafenib and PR to regorafenib, and then applied in seven patients with different types of response. Overall, the rate constant of cancer cells production ranged between 0.250–0.372 C × day−1. During therapy, neo-angiogenesis reduction was higher in four CR than in four PR or stable disease (SD) and in two non-responders (median: 83.2% vs. 29.4% vs. 2.0%). Tumor vasculature decay appeared accelerated in CR. We conclude that modeling serological and imaging biomarkers could help personalization of systemic therapy. In advanced HCC, tyrosine-kinase inhibitors obtain partial responses (PR) in some patients and complete responses (CR) in a few. Better understanding of the mechanism of response could be achieved by the radiomic approach combining digital imaging and serological biomarkers (α-fetoprotein, AFP and protein induced by vitamin K absence-II, PIVKA-II) kinetics. A physic-mathematical model was developed to investigate cancer cells and vasculature dynamics in three prototype patients receiving sorafenib and/or regorafenib and applied in seven others for validation. Overall four patients showed CR, two PR, two stable-disease (SD) and two progressive-disease (PD). The rate constant of cancer cells production was higher in PD than in PR-SD and CR (median: 0.398 vs. 0.325 vs. 0.316 C × day−1). Therapy induced reduction of neo-angiogenesis was greater in CR than in PR-SD and PD (median: 83.2% vs. 29.4% and 2.0%), as the reduction of cell-proliferation (55.2% vs. 7.6% and 0.7%). An additional dose-dependent acceleration of tumor vasculature decay was also observed in CR. AFP and cancer cells followed the same kinetics, whereas PIVKA-II time/dose dependent fluctuations were influenced also by tissue ischemia. In conclusion, pending confirmation in a larger HCC cohort, modeling serological and imaging biomarkers could be a new tool for systemic therapy personalization. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess diagnostic accuracy and reliability of narrow band imaging (NBI) in the differential diagnosis of laryngeal premalignant lesion, early cancers and recurrences. Material and methods: We enrolled 231 patients who underwent endoscopic examination with white light endoscopy (WLE) + NBI and divided them into two groups, group A, without previous radiochemotherapy and group B, with previous radiochemotherapy. When indicated, we performed surgical biopsies to evaluate sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and likelihood of endoscopic examination comparing WLE alone and WLE + NBI. Results: A positive NBI lesion, compared with a negative NBI lesion, had a 29.68 (group A) and 13.96 (group B) times higher probability to be histologically positive (i.e., confirmed) compared with WLE alone improving the diagnostic accuracy. In group A, the NBI mode showed excellent sensitivity (95.0%), which was higher than WLE 2 mode (77.5%). However, the greatest differences were recorded regarding specificity (96.8% vs. 40.6%). In group B, both NBI alone and WLE + NBI mode showed a 94.1% specificity compared with WLE alone, which had a maximum specificity of 85.3%. The mode comparison between NBI and WLE in both groups showed a statistically significant difference, with p-values <0.0001. Conclusions: NBI represents a reliable technology in challenging situations, especially in the context of post-radiotherapy or post-surgical mucosal changes showing a high NPV. NBI could reduce the number of unnecessary biopsies related to increased microvascular anomaly revelation, which could help to identify early-stage lesions suitable for minimally invasive surgery and, consequently, decrease hospital admissions. [ABSTRACT FROM AUTHOR]

Biologically inspired to mammalian olfactory system, electronic noses became popular during the last three decades. In literature, as well as in daily practice, a wide range of applications are reported. Nevertheless, the most pioneering one has been (and still is) the assessment of the human breath composition. In this study, we used a prototype of electronic nose, called Wize Sniffer (WS) and based it on an array of semiconductor gas sensor, to detect ammonia in the breath of patients suffering from severe liver impairment. In the setting of severely impaired liver, toxic substances, such as ammonia, accumulate in the systemic circulation and in the brain. This may result in Hepatic Encephalopathy (HE), a spectrum of neuro–psychiatric abnormalities which include changes in cognitive functions, consciousness, and behaviour. HE can be detected only by specific but time-consuming and burdensome examinations, such as blood ammonia levels assessment and neuro-psychological tests. In the presented proof-of-concept study, we aimed at investigating the possibility of discriminating the severity degree of liver impairment on the basis of the detected breath ammonia, in view of the detection of HE at its early stage. [ABSTRACT FROM AUTHOR]