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.

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.

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.

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.

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.

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.

Changes in Breathing Patterns after Surgery in Severe Laryngomalacia.

BACKGROUND: Most of the studies regarding the surgical treatment of severe laryngomalacia (LM) have been aimed at describing the efficacy of the treatment in terms of improvement of clinical symptoms or anatomical findings. There are no studies specifically aimed at analyzing the changes in breathing patterns following surgical treatment for severe LM. OBJECTIVE: To review the breathing pattern changes before and after corrective surgery in infants with severe LM. STUDY DESIGN: A series of retrospective cases at a tertiary referral children's hospital. METHODS: Retrospective chart review of 81 infants who underwent supra-glottoplasty (SGP) for severe laryngomalacia between 2011 and 2020 at Bambino Gesù Children's Hospital of Rome, Italy. Among the patients, 47 (58%) were male and 34 (42%) were female. Twenty-one patients (26%) had one or more comorbidities condition. The data collected included age, symptoms, a polysomnography/pulse oximetry study, growth rate, the findings from flexible endoscopy, pre- and post-supra-glottoplasty (SGP) pulmonary function tests (PFTs) and, when indicated, 24 h pH-metry. Breathing patterns were studied during restful, normal sleep, using an ultrasonic flow-meter (Exhalyzer, Viasys) which measured: Tidal Volume (Vt), Respiratory Rate (RR), time to peak expiratory flow/expiratory time ratio (tPTEF/Te, an index of the patency of the lower airways) and mean expiratory/mean inspiratory flow ratio (MEF/MIF, an index of the patency of the upper airways) evaluated before surgical procedure (T1) and 3-6 weeks after (T2). Pre- and post-operative mean data were calculated and comparisons made with a Student T-test. RESULTS: The surgical procedure was well tolerated by all infants and no intraoperative or post-operatory long-term complications were noted. In T1, breathing patterns were characterized by low tidal volume and high tPTEF/Te and MEF/MIF ratios, suggesting a severe reduction in the patency of the upper airways in all patients. After surgery (T2), all the previously mentioned variables significantly improved, reaching normal values for the child's age. CONCLUSIONS: Supra-glottoplasty, as already described in several studies, is a safe and efficient procedure to treat severe laryngomalacia during infancy. The improvement in breathing patterns after surgery was reliably confirmed by a lung function test in our study, which showed the diagnostic value of testing respiratory functionality in the laryngomalacia and comparing them to clinical and endoscopic data. Moreover, considering the results obtained, we also propose the use of this available, dependable test to verify its therapeutic effects (post-surgery) and to monitor future respiratory development in these infants. Moreover, we believe that further studies will provide detailed grading guidelines for gravity of the LM, based on these functional lung tests.

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.

Modeling Hepatocellular Carcinoma Cells Dynamics by Serological and Imaging Biomarkers to Explain the Different Responses to Sorafenib and Regorafenib.

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.

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.

Predictors of Disease Control After Endoscopic Sinus Surgery Plus Long-Term Local Corticosteroids in CRSwNP.

BACKGROUND: in the era of new biological agents it is important to identify patients who may benefit from conventional therapies such as endoscopic sinus surgery (ESS) plus long-term local corticosteroids from those with patterns of inflammation that are more difficult to control post-operatively and who may benefit from other therapies. OBJECTIVE: determine if preoperative assessment of type and grade of inflammation and clinical factors can predict disease control with ESS plus long-term local corticosteroids in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Eighty patients treated with ESS plus mometasone-furoate 200 µg BID for CRSwNP and followed for at least 1 year were enrolled (November 2017-December 2018) in this prospective observational study. Type and grade of inflammation were evaluated preoperatively by nasal cytology. Based on cellular pattern, patients were grouped as neutrophilic (n = 20), eosinophilic (n = 38), or mixed eosinophil-neutrophilic (n = 22). SNOT-22 and Lund-Kennedy Endoscopic Score were evaluated at baseline and at 3, 6, 9, and 12 months after surgery and used to define disease control. RESULTS: The cumulative probability of remaining free of significant modification of endoscopic score (Lund-Kennedy Endoscopic Score >2) at 3, 6, 9, and 12 months was 0.84, 0.76, 0.71, and 0.68, respectively. At 12-month postoperative evaluation good disease control was observed in 54 of 80 patients (67.5%). Compared to those with good post-operative disease control, those with poor control had a significantly higher pre-operative mean count of eosinophils and neutrophils (p < 0.05). The preoperative inflammatory pattern was associated with relative risk of poor control: neutrophilia (RR: 3.10; CI:1.24-7.71), eosinophilia (RR:8.42; CI:2.72-15.12), and mixed eosinophilic and neutrophilic (RR:25.11; CI:19.41-30.01). We also confirmed that asthma, allergy, blood eosinophilia, and ASA triad could predict poor control. CONCLUSIONS: The type and load of inflammation evaluated preoperatively and selected clinical factors can predict poor control of CRSwNP treated with ESS and local corticosteroids.

Functional results of exclusive interventional radiotherapy (brachytherapy) in the treatment of nasal vestibule carcinomas.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Surgical Options for Pediatric Bilateral Vocal Cord Palsy: State of the Art.

Management of pediatric bilateral vocal cord palsy (BVCP) is a controversial and challenging topic. It may represent a severe obstructive condition usually associated with respiratory distress, and, in such condition, tracheostomy has been considered the gold standard for a long time. Many surgical options have been described and used to increase the glottic space in BVCP (1), with ongoing research of less invasive techniques. The challenge and current trend in our department and in many major pediatric centers is to avoid tracheotomy through an early treatment. Many techniques introduced in the last decade reduced the number of tracheotomies and increased the decannulation rate. Furthermore, we observed a recent increase in attention to preserve the quality of the voice with new techniques, such as endoscopic arytenoid abduction lateropexy which is in our opinion an important innovation to improve glottic space with satisfactory voice results. We present a review of the literature about the evolution of the treatment options for pediatric BVCP during the years.

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.

Determinants of glomerular filtration rate following bariatric surgery in individuals with severe, otherwise uncomplicated, obesity: an observational, prospective study.

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 m2; hyperfiltration (>120 ml/min/1.73 m2) 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 m2 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 m2 (median value) showed, after 48 months, an average loss of -8.3 ± 2.2 ml/min/1.73 m2, while those with eGFR <100 exhibited a slight increase (+1.8 ± 2.3 ml/min/1.73 m2, 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.

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.

Adipocyte P2X7 receptors expression: a role in modulating inflammatory response in subjects with metabolic syndrome?

OBJECTIVE: P2X(7) receptor (P2X(7)R), 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 P2X(7)R 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); P2X(7)R expression (realtime-PCR, Western blot and immunofluorescence); P2X(7)R 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. P2X(7)R 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 P2X(7)R 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 P2X(7)R blocker, or by P2X(7)R gene silencing. The inflammasome was more activated in MS than in CTL adipocytes. CONCLUSION: Human adipocytes express functionally active P2X(7)R, which modulate the release of inflammatory cytokines, at least in part via inflammasome activation. Adipocytes from MS patients show an enhanced P2X(7)R expression, which might contribute to the subclinical inflammatory status characterizing these patients and conferring them an increased CV risk.