Simple proxies of insulin resistance identify obese metabolic dysfunction-associated fatty liver disease subjects with advanced liver disease.

AIMS: Insulin resistance (IR) plays a pivotal role in the pathogenesis of Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD), which can progress to liver fibrosis. We examined the relationship of different IR scores with markers of MAFLD severity in obese individuals. MATERIALS AND METHODS: In this retrospective observational study, 346 non-diabetic, overweight/obese individuals with newly diagnosed MAFLD (age 50.2 ± 13.3 years, 34% females, BMI 30.8 ± 4.4 kg/m2 ) underwent liver stiffness (LS) and controlled attenuation parameter (CAP) measurements by Fibroscan® to assess liver fibrosis and steatosis. Biochemical data were collected to calculate surrogate markers of IR (Homoeostasis model assessment - insulin resistance index [HOMA-IR], triglyceride-glucose index, triglyceride by HDL ratio), liver fibrosis (Nonalcoholic Fatty Liver Diseases fibrosis score, fibrosis-4 score, Aspartate aminotransferase to platelet ratio index) and steatosis (fatty liver index, hepatic steatosis index). RESULTS: All three IR scores were associated with CAP, while only HOMA-IR positively correlated with LS (r = 0.275, p < 0.0001), independent of age and sex, BMI, transaminases, and fibrosis markers. Insulin-resistant individuals (HOMA-IR >2.5, n = 165) had higher liver enzymes, CAP and LS, with a 4-fold increased risk of severe liver disease (LS >9.7 kPa, OR 4.42[1.95-10.01], p = 0.0002). Among HOMA-IR components, fasting plasma insulin (FPI) was independently associated with LS (r = 0.270, p < 0.0001). ROC AUC for HOMA-IR and FPI to predict severe liver disease were virtually identical (0.748 and 0.758, respectively). CONCLUSIONS: HOMA-IR is independently associated with non-invasive markers of MAFLD severity in overweight/obese individuals. This relationship is largely mediated by hyperinsulinemia, regardless of BMI. Measuring insulin levels in MAFLD individuals might be useful to identify those at risk of liver fibrosis.

Foreign body aspiration in children: our pediatric tertiary care experience.

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.

The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage.

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.

Functional and aesthetic results after septorhinoplasty and concomitant radiofrequency of the inferior turbinate: is there a role for patient reported outcome measures (PROMs)?

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.

An E-Nose for the Monitoring of Severe Liver Impairment: A Preliminary Study.

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.

Long-term outcome of inactive and active, low viraemic HBeAg-negative-hepatitis B virus infection: Benign course towards HBsAg clearance.

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≤1000IU/HBV-DNA≤2000IU/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.

The complex P2X7 receptor/inflammasome in perivascular fat tissue of heavy smokers.

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 P2X7 receptor (P2X7 R)-inflammasome complex, crucial in determining IL-1ß 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 P2X7 R-inflammasome in this picture. SUBJECTS AND METHODS: TNFα, IL-6, RBP4, MCP-1, as well as P2X7 R and inflammasome components NLRP3, ASC, caspase-1 and IL-1ß 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 P2X7 R and inflammasome components; via P2X7 R activation, it released more IL-1ß and IL-18, whose serum levels were also higher in Smok than in No-Smok. Linear correlations of NLRP3 with P2X7 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 P2X7 R-inflammasome complex; the effect on adipocytokines more related to insulin resistance and metabolic abnormalities appears trivial.

Response to semaglutide of non-drinker subjects with type 2 diabetes.

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.

Nutritional intervention in the management of non-alcoholic fatty liver disease.

Lifestyle modification is the primary intervention to control NAFLD progression, but despite evidence-based effectiveness it is difficult to distinguish the benefits of nutrition from physical activity and the optimal diet composition is not established. Macronutrients as saturated fatty acids, sugars and animal proteins are harmful in NAFLD and the Mediterranean Diet reducing sugar, red meat and refined carbohydrates and increasing unsaturated-fatty-acids was reported to be beneficial. However one size cannot fit all since NAFLD is a multifaceted syndrome encompassing many diseases of unknown etiologies, different clinical severity and outcomes. Studies of the intestinal metagenome, provided new insights into the physio-pathological interplay between intestinal microbiota and NAFLD. How much the microbiota heterogeneity can influence response to diet remains unknown. New knowledge indicates that AI guided personalized nutrition based on clinic-pathologic and genetic data combined with pre/post nutritional intervention gut metagenomics/metabolomics will be part of the future management of NAFLD.

Pediatric Bilateral Vocal Cord Immobility: New Treatment With Preservation of Voice.

OBJECTIVES: Pediatric bilateral vocal cord immobility (BVCI) represents a severe life-threatening condition that often causes severe dyspnea. Endoscopic arytenoid lateral abduction (EALA) is a relatively new, secure, minimal-invasive surgical technique. The present prospective observational study aims to evaluate the effects of EALA in terms of respiratory function, voice quality, and swallowing capabilities. METHODS: Twenty-one pediatric patients with BVCI underwent EALA. Eleven out of 21 patients had tracheostomy at the time of surgery. Pre and postoperative functional assessments included endoscopic evaluation, maximum phonation time, pediatric Voice Handicap Index (pVHI), GIRBAS Scale criteria, and Montreal Children's Hospital Feeding scale (MCH-Feeding scale). peak tidal inspiratory flow or peak inspiratory flow (PIF) and number of desaturations/hour (ODI/h) were evaluated in patients without tracheostomy. RESULTS: Postoperative endoscopy showed glottic airway improvement in all patients. Average time for decannulation was 4.6 weeks. One patient has not yet been decannulated. No major complications occurred. In patients without tracheostomy, we observed a significant improvement of ODI/h and PIF after surgery (p < 0.05) as expected. PVHI, MCH-Feeding scale, and GIRBAS score significantly worsened 1 month after surgical intervention (p < 0.05). One year after surgery, however, all values, except for B and A parameters of the GIRBAS score, returned to levels comparable to those preoperative. CONCLUSIONS: EALA represents a simple, safe and effective solution in pediatric patients with BVCI, avoiding tracheostomy, allowing early decannulation, preserving swallowing function, and maintaining good quality voice. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2325-2332, 2023.

Highly dynamic changes of regional HBV epidemiology over two decades.

BACKGROUND & AIM: HBV epidemiology is highly heterogeneous and rapidly evolving worldwide: we studied its last two-decades dynamics in a large single center cohort. METHODS: In all consecutive HBsAg-positive subjects firstly admitted (2000-2019) at the Pisa-University-Hospital Hepatology-Referral-Center, demographic, virologic and clinical variables were analyzed by admission decade (2000-2009 vs 2010-2019) and origin (Italian vs non-Italian natives). RESULTS: Of 2003, 1878 (93.7%) subjects were eligible: 1798(95.7%) with HBV-chronic [126(7%) HDV, 72(4%) HCV, 11(0.6%) HIV co-infected] and 80(4.3%) HBV-primary infections (93.7% Italians). Among 1589(88.4%) mono-infected, 496(31.2%) were immigrants, younger than Italians [34.0(5.1-77.1)-52.5(10.0-87.2) years], with female prevalence [204/496(41.1%)-340/1093(31.1%); p<0.001] increasing overtime (14.6-45.0%; p<0.001). Italians aged across decades [50.3(11.1-87.2)-56.2(10.0-86.7) years; p<0.001], HBeAg-positivity remained stable (12.3-14.5%) and acute hepatitis increased (4.0-8.0%; p = 0.003). CHB declined [439/721(60.9%)-320/868(36.9%); p<0.001] whereas HBeAg-negative infection increased [277/626(44.2%)-538/755(71.3%); p<0.001]. Cirrhosis declined [195/721(27.0%)-125/868(14.4%); p<0.001], except in anti-HDV-patients [93/126(73.8%); 42(45.1%) non-Italians], younger than HBV-mono-infected (47.4-57.6 years; p<0.001). CONCLUSION: Effective preventive health care policies and immigration flows account for increasing prevalence of HBeAg-negative infection across the last two decades. Antiviral therapy mitigated disease progression in aging Italian CHB but not in CHD patients, mainly young immigrants, emphasizing the unmet need of effective CHD therapies; HBeAg-positive CHB and acute hepatitis B persist in non-vaccinated Italian adults, prompting vaccination in the elderly with risky behaviors.

Functional ice cream health benefits and sensory implications.

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.

Effects of Different Scan Projections on the Quantitative Ultrasound-Based Evaluation of Hepatic Steatosis.

Non-alcoholic fatty liver disease (NAFLD) is becoming a global public health issue and the identification of the steatosis severity is very important for the patients' health. Ultrasound (US) images of 214 patients were acquired in two different scan views (subcostal and intercostal). A classification of the level of steatosis was made by a qualitative evaluation of the liver ultrasound images. Furthermore, an US image processing algorithm provided quantitative parameters (hepatic-renal ratio (HR) and Steato-score) designed to quantifying the fatty liver content. The aim of the study is to evaluate the differences in the assessment of hepatic steatosis acquiring and processing different US scan views. No significant differences were obtained calculating the HR and the Steato-score parameters, not even with the classification of patients on the basis of body mass index (BMI) and of different classes of steatosis severity. Significant differences between the two parameters were found only for patients with absence or mild level of steatosis. These results show that the two different scan projections do not greatly affect HR and the Steato-score assessment. Accordingly, the US-based steatosis assessment is independent from the view of the acquisitions, thus making the subcostal and intercostal scans interchangeable, especially for patients with moderate and severe steatosis.

Elective Neck Dissection during Salvage Total Laryngectomy: Personal Experience.

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.

Pediatric Voice Handicap Index (pVHI): A Tool for Evaluating the Reliability and Validity of Voice Therapy in Children With Benign Vocal Fold Nodules.

OBJECTIVES: benign vocal fold lesions (BVFLs) represent the most common etiology of voice disorders in paediatric population, cause of dysphonia by preventing full vocal fold closure and modifying vibratory characteristics. Of those pathologies, vocal fold nodules represent almost 63% of the cases in children between 0-14 years. Management may include a combination of phonosurgery, voice therapy and pharmacological treatment, but almost 95% of otolaryngologists recommend voice therapy as primary treatment. The Pediatric Voice Handicap Index (pVHI) is nowadays widely used and accepted in the evaluation and monitoring of paediatric patients with dysphonia. The aim of our study was to demonstrate the reliability and validity of PVHI in the evaluation of the effects of voice therapy as treatment of vocal fold nodules in the paediatric population. PATIENTS AND METHOD: in this retrospective chart review twenty-seven (27) dysphonic patients with bilateral vocal fold nodules were treated with behavioral voice therapy approaches, and the PVHI surveys was administered to each patient parent's before and after therapy. The age of the patients ranged from 4 to 14 years (mean age 8.7 y-o); 17 (63%) were male and 10 (37%) females. RESULTS: according to our results, behavioral voice therapy effectively improved pVHI scores from pre- to post-treatment in paediatric patients with bilateral vocal fold nodules.

Predictive Power of Tissue and Circulating Biomarkers for the Severity of Biopsy-Validated Chronic Liver Diseases.

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.

Different Kinetics of HBV-DNA and HBsAg in HCV Coinfected Patients during DAAs Therapy.

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.

3D bioprinting in airway reconstructive surgery: A pilot study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. LEVEL OF EVIDENCE: NA.

Role of Narrow Band Imaging Technology in the Diagnosis and Follow up of Laryngeal Lesions: Assessment of Diagnostic Accuracy and Reliability in a Large Patient Cohort.

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.

Stapler Use in Salvage Total Laryngectomy: A Useful Tool?

OBJECTIVES/HYPOTHESIS: To analyze stapler benefits in salvage total laryngectomy in terms of surgical time, hospitalization length, oral feeding time, and occurrence of pharyngocutaneous fistula, and to evaluate risk factors for its onset. STUDY DESIGN: Retrospective analysis. METHODS: One hundred fourteen patients affected by endolaryngeal squamous cell carcinoma who underwent salvage total laryngectomy following primary treatment failure were reviewed. We divided patients into two groups based on type of pharyngeal suture performed: mechanical suture with stapler (group A) and manual suture (group B). These two groups were compared for surgical time, start of oral feeding, hospitalization length, surgical margins and pharyngocutaneous fistula incidence considering its relationship with diabetes mellitus, nutritional status, primary treatment, and neck dissection. RESULTS: In group A and group B, oral feeding restarting time was 15 ± 9.33 versus 20.03 ± 13.81 days, hospitalization was 17.63 ± 10.08 versus 23.72 ± 14.29 days, and surgery lasted 268.39 ± 76.93 versus 294.26 ± 140.58 minutes, respectively (P < .05). Surgical margins resulted infiltrated in two patients (4.3%) in group A and 12 patients in group B (17.6%) (P = .03). Twenty-one patients (18.4%) presented with pharyngocutanoeus fistula. In group A and group B the incidence of fistula was 15.2% and 20.6%, respectively (P = .468). Fistula occurred in 7 of 18 diabetic patients (38.9%) and 14 of 96 (14.6%) nondiabetic patients (P = .015). Nineteen fistulas (90.5%) occurred in patients who had undergone previous radiation treatment (P = .013). CONCLUSIONS: Using a stapler shortened operative time and hospitalization, while also providing a faster restart of oral feeding. Moreover, mechanical pharyngeal suture seems to decrease fistula rate even though its prevention role in salvage laryngectomy should be confirmed by further studies. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E473-E478, 2021.