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Objective This randomized, double-blind, placebo-controlled crossover study assessed the efficacy of topical tocopherol acetate compared with placebo in easing oral discomfort in patients with reticular oral lichen planus ( ROLP). Materials and Methods Thirty-four patients with clinically diagnosed and histologically confirmed ROLP were randomly assigned to two groups, which received first one of two treatments (treatment 1 or 2) for a month, then the other (treatment 2 or 1) for another month, with a two-week washout between them. One treatment contained tocopherol acetate and the other only liquid paraffin. The primary outcome was less discomfort, measured on a visual analog scale ( VAS). Secondary outcomes were as follows: length of striae measured and photographed at each follow-up; surface area of lesions; and a modified Thongprasom score. Results No statistically significant differences emerged between the two treatments (1 vs 2) in terms of VAS scores ( P > 0.05; 0.8624) or length of striae ( P = 0.0883). Significant differences were seen for surface area of lesions ( P < 0.05, P = 0.0045) and modified Thongprasom scores ( P = 0.0052). Conclusion The two treatments differed only in terms of the surface area of the lesions and Thongprasom scores, not in VAS scores for discomfort or the length of patients' striae. Topical tocopherol proved effective in the treatment of ROLP. [ABSTRACT FROM AUTHOR]

BACKGROUND: Quick change (QC) and double pumping (DP) are common methods of substituting the infusion of inotropes given through intravenous pump. AIMS: The aim of the study was to compare two methods in respect with the variation in mean arterial pressure (MAP). The hypothesis was that the DP method could be the most effective in achieving haemodynamic stability. DESIGN: The study is a randomized research in an open randomized clinical trial. METHODS: The study took place at the Paediatric Intensive Care Unit of Padua Hospital. It considered patients of 0-36 months, not premature, treated with inotropic infusion with monitoring of blood pressure. The research obtained the approval of the Hospital Research Ethics committee and parents signed informed consent. Comparison of the two groups made use of the Wilcoxon test for the continuous variables and the Fisher's exact test for the comparison of frequencies, at significance value of 5%. The data were registered in an Excel spreadsheet and analysed with SAS. RESULTS: The sample comprised 30 patients of age between 1 and 27 months, of whom 13 (43%) were male. They were all affected by cardiac, respiratory or infective pathology, all of them intubated and on artificial respiratory support, sedated and infused with dopamine. The characteristics of the patients of the two groups did not differ significantly. The percentage variation of the baseline value of MAP after 30 min from starting the treatment between the two methods was not statistically significant (p = 0.85). The 95% confidence interval for the difference in the percentage variation of MAP between the two groups was (-3.1, +3.7). From a clinical perspective, the methods are to be considered equivalent. CONCLUSIONS: The study was conducted on a limited sample; no statistically significant differences were detected; QC is the quickest and more cost-effective method. [ABSTRACT FROM AUTHOR]

Background & Aims: The underlying mechanisms and clinical impact of portal microthrombosis in severe COVID-19 are unknown. Intrapulmonary vascular dilation (IPVD)-related hypoxia has been described in severe liver diseases. We hypothesised that portal microthrombosis is associated with IPVD and fatal respiratory failure in COVID-19., Methods: Ninety-three patients who died from COVID-19 were analysed for portal microvascular damage (histology), IPVD (histology and chest-computed tomography, CT), and hypoxemia (arterial blood gas). Seventeen patients who died from COVID-19-unrelated pneumonia served as controls. Vascular lesions and microthrombi were phenotyped for endothelial (vWF) and pericyte (αSMA/PDGFR-β) markers, tissue factor (TF), viral spike protein and nucleoprotein (SP, NP), fibrinogen, and platelets (CD41a). Viral particles in vascular cells were assessed by transmission electron microscopy. Cultured pericytes were infected with SARS-CoV-2 to measure TF expression and tubulisation of human pulmonary microvascular endothelial cells was assessed upon vWF treatment., Results: IPVD was present in 16/66 patients with COVID-19, with available liver and lung histology, and was associated with younger age (62 vs. 78 years-old), longer illness (25 vs. 14 days), worsening hypoxemia (PaO 2 /FiO 2 from 209 to 89), and an increased requirement for ventilatory support (63% vs. 22%) compared to COVID-19/Non-IPVD. IPVD, absent in controls, was confirmed by chest CT. COVID-19/IPVD liver histology showed portal microthrombosis in >82.5% of portal areas, with a thicker wall of αSMA/PDGFR-β + /SP + /NP + pericytes compared with COVID-19/Non-IPVD. Thrombosed portal venules correlated with αSMA + area, whereas infected SP + /NP + pericytes expressed TF. SARS-CoV-2 viral particles were observed in portal pericytes. In vitro SARS-CoV-2 infection of pericytes upregulated TF and induced endothelial cells to overexpress vWF, which expanded human pulmonary microvascular endothelial cell tubules., Conclusions: SARS-CoV-2 infection of liver pericytes elicits a local procoagulant response associated with extensive portal microthrombosis, IPVD and worsening respiratory failure in fatal COVID-19., Impact and Implications: Vascular involvement of the liver represents a serious complication of COVID-19 infection that must be considered in the work-up of patients with long-lasting and progressively worsening respiratory failure, as it may associate with the development of intrapulmonary vascular dilations. This clinical picture is associated with a procoagulant phenotype of portal venule pericytes, which is induced by SARS-CoV-2 infection of pericytes. Both observations provide a model that may apply, at least in part, to other vascular disorders of the liver, featuring obliterative portal venopathy, similarly characterised at the clinical level by development of hypoxemia and at the histological level by phlebosclerosis and reduced calibre of the portal vein branches in the absence of cirrhosis. Moreover, our findings shed light on an overlooked player in the pathophysiology of thrombosis, i.e. pericytes, which may present a novel therapeutic target., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The diagnosis of celiac disease (CD) is still challenging and tests that show an activation of the immune system against gluten are required. IgA antiendomysial antibodies detection in the supernatant of intestinal biopsies by immunofluorescence technique (AEA-biopsy) is a promising diagnostic tool. The aim of the present study was to evaluate the diagnostic accuracy of AEA-biopsy in a pediatric population with suspected CD., Methods: All children who underwent upper gastrointestinal endoscopy at the Unit of Pediatrics of Treviso Hospital were enrolled and divided into 4 groups: classical CD, CD excluded, potential CD and control group. For each patient, serum autoantibodies and histological evaluation were determined. Two additional biopsy samples were taken to test for presence of AEA., Results: A total of 92 patients were enrolled. All the classical CD cases (38) had a positive AEA-biopsy. In the CD excluded group (10 in total) AEA-biopsy was negative in all patients except 1. Among potential CD patients (which were 14), AEA-biopsy was negative in 4. In the control group (30 patients) AEA-biopsy was negative in all patients except 1. The sensitivity and specificity of AEA-biopsy were 100% and 96% respectively., Conclusions: AEA-biopsy has an excellent diagnostic accuracy in a routine clinical setting.

While concerns about high-flow nasal cannula oxygen (HFNC) overuse and associated increased use of hospital resources are rapidly spreading, a two-tiered approach in its use is recommended by recent bronchiolitis guidelines. However, data on its effects in practice have not been reported. We aimed to analyze the trends in use of HFNC, hospitalizations, length of stay (LOS), and intensive care unit (ICU) admissions for bronchiolitis in a tertiary care center using a two-tiered HFNC approach since its introduction in practice. We retrospectively included data of children < 12 months of age who presented to the Paediatric Emergency Department (PED) and were hospitalized for bronchiolitis at our institution in the epidemic season between October 1st and April 30th during the years 2012-2023 and compared the clinical data across the years. Of the 687 hospitalized children included, 79.9% required oxygen supplementation. Use of HFNC significantly increased since its implementation (from 25% in 2012-2013 to over 60% since 2019-2020, p < 0.0001) and was most frequently administered as rescue treatment (in 57.5% of patients). There was no increased trend in ICU admissions (between 1.5% and 10.0% of hospitalizations across seasons, p = 0.40), while LOS, after increasing between 2013 and 2016 (medians between 4.0 and 5.4 days), remained stable thereafter (medians between 3.8 and 4.3 days)., Conclusions: The use of HFNC according to a two-tiered approach does not appear to be associated with an increase in ICU utilization or LOS., What Is Known: • Bronchiolitis is one of the most common reasons for hospitalization in infants. • Use high-flow nasal canulae oxygen (HFNC) has rapidly spread outside the intensive care unit (ICU) to treat infants with bronchiolitis, although increasing evidence has dampened the initial enthusiasm about their effectiveness. • Concerns nowadays are rising about HFNC overuse and associated increased use of hospital resources, including escalation of care to ICU., What Is New: • A more selective use of HFNC according to a "two-tiered approach", intended as a second-line rescue treatment in non-severely ill children who fail standard oxygen therapy, is not associated with increased ICU and length of hospital stay., (© 2024. The Author(s).)

Importance: The 2022 Barcelona Clinic Liver Cancer algorithm currently discourages liver resection (LR) for patients with multinodular hepatocellular carcinoma (HCC) presenting with 2 or 3 nodules that are each 3 cm or smaller., Objective: To compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC., Design, Setting, and Participants: This cohort study is a retrospective analysis conducted using data from the HE.RC.O.LE.S register (n = 5331) for LR patients and the ITA.LI.CA database (n = 7056) for PRFA and TACE patients. A matching-adjusted indirect comparison (MAIC) method was applied to balance data and potential confounding factors between the 3 groups. Included were patients from multiple centers from 2008 to 2020; data were analyzed from January to December 2023., Interventions: LR, PRFA, or TACE., Main Outcomes and Measures: Survival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes., Results: A total of 720 patients with early multinodular HCC were included, 543 males (75.4%), 177 females (24.6%), and 350 individuals older than 70 years (48.6%). There were 296 patients in the LR group, 240 who underwent PRFA, and 184 who underwent TACE. After MAIC, LR exhibited 1-, 3-, and 5-year survival rates of 89.11%, 70.98%, and 56.44%, respectively. PRFA showed rates of 94.01%, 65.20%, and 39.93%, while TACE displayed rates of 90.88%, 48.95%, and 29.24%. Multivariable Cox survival analysis in the weighted population showed a survival benefit over alternative treatments (PRFA vs LR: hazard ratio [HR], 1.41; 95% CI, 1.07-1.86; P = .01; TACE vs LR: HR, 1.86; 95% CI, 1.29-2.68; P = .001). Competing risk analysis confirmed a lower risk of cancer-related death in LR compared with PRFA and TACE., Conclusions and Relevance: For patients with early multinodular HCC who are ineligible for transplant, LR should be prioritized as the primary therapeutic option, followed by PRFA and TACE when LR is not feasible. These findings provide valuable insights for clinical decision-making in this patient population.

Different inflammatory endotypes reflect the heterogeneity of chronic rhinosinusitis with nasal polyps' (CRSwNPs) clinical presentation. This retrospective study aimed to analyze the distribution of polyps in nasal cavities and paranasal sinuses to establish a possible association between CRSwNP endotypes, prognosis, and polyps' extension. This study included 449 adult patients who underwent endoscopic sinus surgery for CRSwNPs between 2009 and 2022. Patients were categorized based on the number of paranasal sinuses involved by polyps. Statistical analyses, including Cox regression, were performed to identify associations between demographic, clinical, and histopathological factors and disease recurrence. CRSwNP patients were stratified into four groups based on the extent of polyp involvement. Asthma and acetylsalicylic acid (ASA) sensitivity were associated with more sinuses involved ( p -values = 0.0003 and 0.0037, respectively). Blood eosinophil counts increased with the number of sinuses affected ( p -value < 0.0001). The distribution of eosinophilic and non-eosinophilic histotypes varied significantly among these groups ( p -value < 0.0001). The risk of CRSwNP recurrence was higher in patients with asthma, higher basophil percentages, and eosinophilic histotype ( p -value 0.0104, 0.0001, 0.0118, and 0.0104, respectively). This study suggests a positive association between the number of paranasal sinuses involved by polyps and the severity of CRSwNPs, particularly in patients with eosinophilic histotype, asthma, and ASA sensitivity.

Cardiorespiratory fitness (CRF) is a strong predictor of morbidity and mortality in patients with obesity. This study investigates the CRF range and its clinical determinants in patients with obesity. Moreover, a practical proposal for CRF interpretation is provided. In this study, 542 patients (69% females) with BMI ≥ 30 kg/m 2 performed an incremental cardiopulmonary exercise test (CPET). Patients had a median (IQR) age of 47.0 (6.2) years with a mean BMI of 41.7 ± 6.7 kg/m 2 . Normal values curves of VO 2 peak/kg showed a median (IQR) of 20.3 (37.6) mL/min/kg. The lower-quartile threshold of VO 2 peak/kg was at 17.9 mL/min/kg. Analysis of covariance revealed that VO 2 peak/kg inversely correlates with age and BMI with a significant age × BMI interaction effect (all p < 0.0001); as BMI class increases, CRF decreases, but a smaller age-related decline in VO 2 peak/kg is observed. A multivariate logistic regression demonstrated that belonging to the lower quartile of VO 2 peak/kg was independently determined by age (OR 2.549, 95% CI 1.205-5.392, p < 0.0001) and BMI (OR 5.864, 95% CI 2.920-11.778, p < 0.0001) but not by comorbidities. At very high BMI, the effect of age on functional capacity is lower, suggesting that BMI acts as an "aging factor" on CRF. Age and BMI, but not comorbidities, are independent determinants of low VO 2 peak/kg.

Importance: Deviations from international resuscitation guidelines during the management of pediatric cardiac arrest are frequent and affect clinical outcomes. An interactive tablet application (app), PediAppRREST, was developed to reduce guideline deviations during pediatric cardiac arrest., Objective: To assess the effectiveness of PediAppRREST in improving the management of simulated in-hospital pediatric cardiac arrest., Design, Setting, and Participants: This multicenter 3-group simulation-based randomized clinical trial was conducted from September 2020 to December 2021 at 4 Italian university hospitals (Padua, Florence, Rome, Novara). Participants included residents in pediatrics, emergency medicine, and anesthesiology. Analyses were conducted as intention-to-treat. Data were analyzed from January to June 2022., Interventions: Teams were randomized to 1 of 3 study groups: an intervention group that used the PediAppRREST app; a control group that used a paper-based cognitive aid, the Pediatric Advanced Life Support (PALS) pocket card; and a control group that used no cognitive aids. All the teams managed the same standardized simulated scenario of nonshockable pediatric cardiac arrest., Main Outcomes and Measures: The primary outcome was the number of deviations from guidelines, measured by a 15-item checklist based on guideline recommendations. The main secondary outcomes were quality of chest compressions, team clinical performance (measured by the Clinical Performance Tool), and perceived team leader's workload. Study outcomes were assessed via video reviews of the scenarios., Results: Overall 100 teams of 300 participants (mean [SD] age, 29.0 [2.2] years; 195 [65%] female) were analyzed by intention-to-treat, including 32 teams randomized to the PediAppRREST group, 35 teams randomized to the PALS control group, and 33 teams randomized to the null control group. Participant characteristics (210 pediatric residents [70%]; 48 anesthesiology residents [16%]; 42 emergency medicine residents [14%]) were not statistically different among the study groups. The number of deviations from guidelines was significantly lower in the PediAppRREST group than in the control groups (mean difference vs PALS control, -3.0; 95% CI, -4.0 to -1.9; P < .001; mean difference vs null control, -2.6; 95% CI, -3.6 to -1.5; P < .001). Clinical Performance Tool scores were significantly higher in the PediAppRREST group than control groups (mean difference vs PALS control, 1.4; 95% CI, 0.4 to 2.3; P = .002; mean difference vs null control, 1.1; 95% CI, 0.2 to 2.1; P = .01). The other secondary outcomes did not significantly differ among the study groups., Conclusions and Relevance: In this randomized clinical trial, the use of the PediAppRREST app resulted in fewer deviations from guidelines and a better team clinical performance during the management of pediatric cardiac arrest., Trial Registration: ClinicalTrials.gov Identifier: NCT04619498.

Introduction: The progressive loss of skeletal muscle mass, strength, and function that frequently occurs as people get older is referred to as sarcopenia. Elderly musculoskeletal aging, sarcopenia, and obesity are all intimately connected. Our study's aim is to investigate the prevalence of sarcopenia in a real cohort of patients over 65 with musculoskeletal conditions referring to a Rehabilitation Unit. The secondary aim of our study is to investigate associations between sarcopenia and alterations in nutritional status and Body Mass Index (BMI). Finally, quality of life and global health has been investigated in our population., Materials and Methods: From January 2019 to January 2021, 247 patients over 65 years old with musculoskeletal concerns were enrolled and participated in an observational study. As outcome measures, the Mini Nutritional Assessment (MNA), the 12-Item Short Form Health Survey (SF-12), and the Cumulative Illness Rating Scale Severity Index (CIRS-SI) were used. Additionally, measurements of total skeletal muscle mass (SMM) and appendicular muscle mass (ASMM) using bioelectrical impedance analysis, as well as a hand grip strength test of the non-dominant hand were taken. The Mid Upper Arm Circumference (MUAC) and the Calf Circumference (CC) were measured and recorded as further indications of possible sarcopenia., Results: A percentage of 46.1% of subjects with overt sarcopenia was found and 10.1% showed a severe sarcopenia. Patients with severe sarcopenia showed significantly lower values of BMI and MNA. Additionally, sarcopenic patients showed significantly lower values in MNA when compared to non-sarcopenic patients. Considering SF-12, only the physical score revealed slight significant differences. In particular, patients affected by probable or severe sarcopenia presented a lower value than non-sarcopenic patients. Concerning MUAC and CC, severe sarcopenic patients showed significant lower values for both the body parts., Conclusion: Our study considers a cohort of real-life elderly subjects with musculoskeletal concerns and shows that these subjects are highly susceptible to sarcopenia. Therefore, rehabilitation for elderly patients with musculoskeletal concerns requires to be customized and multidisciplinary. Future research should further investigate these aspects in order to enable the early identification of sarcopenia and the formulation of customized rehabilitative programs. ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Maccarone, Coraci, Bernini, Sarandria, Valente, Frigo, Dionyssiotis and Masiero.)

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and intolerance to cyclooxygenase-1 inhibitors. Interest is emerging in studying the role of circulating inflammatory cells in CRSwNP pathogenesis and its course, as well as their potential use for a patient-tailored approach. By releasing IL-4, basophils play a crucial role in activating the Th2-mediated response. The main aim of this study was to, first, investigate the level of the pre-operative blood basophils' values, blood basophil/lymphocyte ratio (bBLR) and blood eosinophil-to-basophil ratio (bEBR) as predictors of recurrent polyps after endoscopic sinus surgery (ESS) in AERD patients. The secondary aim was to compare the blood basophil-related variables of the AERD series (study group) with those of a control group of 95 consecutive cases of histologically non-eosinophilic CRSwNP. The AERD group showed a higher recurrence rate than the control group ( p < 0.0001). The pre-operative blood basophil count and pre-operative bEBR were higher in AERD patients than in the control group ( p = 0.0364 and p = 0.0006, respectively). The results of this study support the hypothesis that polyps removal may contribute to reducing the inflammation and activation of basophils.

Background: Preterm birth is a risk factor for a child's neurological development. Preterm children have unusual neurodevelopmental profiles with executive, visual-motor functions, fine and gross motor skills, language and behavior that affect learning. In this study, we analyzed the neurodevelopmental outcomes of a cohort of very low birth weight infants admitted to the Treviso Neonatal Intensive Care Unit (NICU) between 2014 and 2016 and followed up to preschool childhood., Method: This is a prospective cohort study. Infants were followed at birth and after NICU discharge at two- and four-year follow-ups. The two-year assessment was conducted with Bayley III, and at four years with the Wechsler Preschool and Primary Scale of Intelligence - III scales and Movement Assessment Battery for Children - 2., Results: The cohort consisted of 207 subjects with a mean gestational age of 28.9 weeks, and a mean birth weight of 1097.2 g. At two years of age, children without disabilities were 90 (59.6%), those with minor disabilities 47 (31.1%), and those with major disabilities 14 (9.3%); at four years, 58.4% of children without previous disabilities, presented problems with verbal tests and manual dexterity: aiming, grasping and balance at movement assessment. There was significant alteration in processing speed (p < 0.001). Furthermore, there was a strong correlation between processing speed and manual dexterity (p < 0.001) and between processing speed and aiming and grasping (p = 0.0059)., Conclusions: We found that more than half the children free of disability at two years, at four years had deficit often involving the oculo-motor coordination and processing speed. These motor profile alterations limit the expression of cognitive abilities and the achievement of expected school performance, thus resulting in behavioral disorders, typical of preterm children. Early professional follow-up could improve the expected educational outcomes., (© 2023. The Author(s).)

Background: Subcortical band heterotopia (SBH) is a rare malformation of the cortical development characterized by a heterotopic band of gray matter between cortex and ventricles. The clinical presentation typically includes intellectual disability and epilepsy., Purpose: To evaluate if the Extended Glasgow Outcome Scale-pediatric version (EGOS-ped) is a feasible tool for evaluating the functional disability of patients with (SBH)., Method: Cross-sectional multicenter study of a cohort of 49 patients with SBH (female n = 30, 61%), recruited from 23 Italian centers., Results: Thirty-nine of 49 (80%) cases showed high functional disability at EGOS-ped assessment. In the poor result subgroup (EGOS-ped >3) motor deficit, language impairment, and lower intelligence quotient were more frequent (P < 0.001, P = 0.02, and P = 0.01, respectively); the age at epilepsy onset was remarkably lower (P < 0.001); and the prevalence of epileptic encephalopathy (West syndrome or Lennox-Gastaut-like encephalopathy) was higher (P = 0.04). The thickness and the extension of the heterotopic band were associated with EGOS-ped score (P < 0.01 and P = 0.02). Pachygyria was found exclusively among patients with poor outcome (P < 0.01)., Conclusions: The EGOS-ped proved to be a reliable tool for stratifying the functional disability of patients with SBH. According to this score, patients could be dichotomized: group 1 (80%) is characterized by a poor overall functionality with early epilepsy onset, thick heterotopic band, and pachygyria, whereas group 2 (20%) is characterized by a good overall functionality with later epilepsy onset and thinner heterotopic band., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Basaloid squamous cell carcinoma (BSCC) is a subtype of squamous cell carcinoma (SCC) associated with a poor prognosis. Tumor-stroma ratio (TSR) has been introduced as a prognostic feature in many solid tumors. TSR was investigated in a series of laryngeal BSCCs and compared with a group of stage-matched conventional SCCs (cSCCs), in both preoperative and surgical specimens, with the intent of ascertaining the more aggressive behavior of BSCC and verifying the presence of stromal-related causes. A series of 14 consecutive laryngeal BSCCs and a control group of 28 stage-matched conventional cSCCs were analyzed. A higher nodal metastasis presence was found in BSCCs (57.1% vs. 28.6%). The recurrence rate was 33.5% and 63.6% in the cSCC and BSCC groups; disease-free survival (DFS) was higher, though not significantly, in patients with cSCC. TSR, large cell nests, and tumor budding showed a moderate to very good agreement, and stroma type a good to very good agreement between biopsies and surgical specimens in the cSCC group. In the BSCC group, agreement was poor to very good for TSR and stroma type, and good to very good for large cell nests and tumor budding. Age was the only feature significant in predicting recurrence in the BSCC group ( p = 0.0235). In cSCC, TSR low/stroma rich cases, when evaluated on biopsies or surgical specimens, were associated with lower DFS ( p = 0.0036; p = 0.0041, respectively). Laryngeal BSCCs showed a lower DFS than cSCCs, even if statistical significance was not reached. TSR, evaluated in laryngeal biopsies and excised tumors, was prognostic in terms of DFS in cSCC but not in BSCC cases.

Objectives: The aim of this study was to assess the predictors of a favourable prognosis of occupational asthma (OA) and the employment status of patients with OA at least 2 years after diagnosis., Methods: We collected data from 204 patients who had a diagnosis of OA confirmed by a positive specific inhalation challenge. We defined OA remission as meeting the following three criteria: no asthma symptoms, no antiasthma therapy for the last year and having normal lung function at the end of follow-up. A logistic regression analysis was performed to estimate the effects of the covariates., Results: At 10.6±7.8-year follow-up, 60 of 204 possible patients participated in the study, and among them 17 showed OA remission. When compared with the 43 patients with persistent OA, these patients exhibited at diagnosis younger age (p=0.0039), shorter duration of symptomatic exposure (p=0.0512), better lung function expressed by higher forced vital capacity (FVC%) predicted (p=0.0164), forced expiratory volume in 1 s (FEV 1 ) % predicted (p=0.0066) and FEV 1 /FVC% (p=0.0132), and less bronchial hyper-responsiveness (p=0.0118). Nevertheless, in the multivariable model, no variables were significantly associated with OA remission. At follow-up, three individuals have retired; among the remaining 57 workers, 91.2% were still employed and 43.8% of them had continued working in the same factory after ceasing exposure to the causative agent., Conclusions: This monocentric study did not identify a strong predictor of OA remission, but documented a high employment rate and a good job preservation over a long timeframe after diagnosis of OA mainly induced by low molecular weight agents., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD), intrinsic asthma, eosinophilic granulomatosis with polyangiitis (EGPA) and odontogenic sinusitis may be associated with nasal polyps. The aim of the study was to compare circulating inflammatory cells and structural histopathology of these groups of nasal polyposis., Methods: We retrospectively evaluated 71 patients with nasal polyps stratified according to the above-mentioned pathogenesis. All patients underwent preoperative laboratory investigations and primary endoscopic sinus surgery. Surgical specimens were submitted to structured histopathological evaluation., Results: The median tissue eosinophil count (cells/HPF) was significantly different between the considered groups of nasal polyposis (p=0.0004). The median of NERD sub-cohort was significantly higher than intrinsic asthma (p=0.0030), odontogenic CRS (p=0.0001) and EGPA ones (p=0.0094). Eosinophilic aggregates positive rate was significantly higher in NERD sub-cohort than in odontogenic CRS (p=0.0072), EGPA (p=0.0497) and asthma (p=0.0188) ones. EGPA sub-cohort had a higher neutrophil infiltrate positive rate than NERD (p=0.0105) and intrinsic asthma ones (p=0.0040). Odontogenic CRS sub-cohort had a higher neutrophil infiltrate positive rate than NERD (p=0.0140) and asthma ones (p=0.0096). EGPA sub-cohort had a higher presence of fibrosis than NERD (p=0.0237) and odontogenic CRS sub-cohort (p=0.0107). Odontogenic sub-cohort had a lower sub-epithelial edema positive rate than NERD (p=0.0028) and asthma (p=0.0149) ones., Conclusions: Structural histopathology may identify nasal polyps histotypes with different morphological patterns. The identified histopathological features can facilitate the recognition of rational therapeutic and follow-up approaches that consider the tissue modifications associated with the response to drugs and surgery., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Several studies investigated the role of fibroblast growth factor 23 (FGF23) in the regulation of renal phosphate excretion in chronic kidney disease (CKD). However, patients with residual urine output (UO) seem to control their serum phosphorus levels better. Our aim was to determine whether FGF23 levels are influenced by dialysis modality and UO. We performed a cross-sectional study in hemodialysis (HD) and peritoneal dialysis (PD) patients. The C-terminal FGF23 (cFGF23) levels were determined in plasma with a two-site enzyme-linked immunosorbent assay. The UO collection referred to an mL/day measurement. All p values were two-sided, and the statistical significance was set at p < 0.05. We enrolled 133 patients (58 HD, 75 PD, UO 70%). The median cFGF23 was significantly higher in HD vs. PD patients (p = 0.0017) and not significantly higher in patients without UO (p = 0.12). We found a negative correlation between cFGF23 and the UO volume (p = 0.0250), but the correlation was not significant when considering the type of dialysis treatment. Phosphorus (ß = 0.21677; p = 0.0007), type of dialysis (ß = −0.68392; p = 0.0003), and creatinine (ß = 0.08130; p = 0.0133) were significant and independent predictors of cFGF23 levels. In conclusion, cFGF23 was significantly higher in HD than in PD patients. We found a significant negative correlation between cFGF23 and the residual UO volume, but the correlation was not significant considering the type of dialysis. Our study reveals that dialysis modality is an independent predictor of FGF23 levels. In particular, PD is associated with lower FGF23 levels than HD.

Purpose: To evaluate outcomes of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) with donor corneas preserved at 31°C in Cornea Syn®, a medium formulated with recombinant human serum albumin (rHSA) to replace foetal calf serum, and deswelled-transported in the xeno-free medium Cornea Trans®., Methods: Prospective, multicentre, open-label study. We evaluated the endothelial cell loss (ECL) as the percentage variation of the endothelial cell density (ECD, cells/mm 2 ) between 6 and 12 months after surgery, corneal transparency and thickness at 12 months, and adverse events within 12 months. Endothelial lenticules of mean 89 μm, ECD ≥ 2300 cells/mm 2 , minimum signs of cell mortality or morphology alterations, were dissected by microkeratome in the eye bank, and grafted in patients ≥ 18 years without corneal neovascularisation, conjunctivalization, or blinking impairment., Results: Thirty-five patients underwent UT-DSAEK, 3 showed primary failure, 1 late failure, and 2 skipped the 6-month visit. We analysed data from 29 patients, 27 with Fuchs endothelial corneal dystrophy (FECD) and 2 with pseudophakic bullous keratopathy (PBK). The median ECL between 6 and 12 months was 2.6% ( p  = .054, CI 0 to 12.5) and the absolute mean (SD) was 158.4 (364.1) cells/mm 2 . After 12 months, 96.5% of corneas were clear, with mean pachymetry of 585.9 (50.4) µm., Conclusions: The ECL rate after UT-DSAEK match overall that observed in DSAEK or UT-DSAEK models of endothelial survival and the overall safety compared that reported for similar follow-up. Corneas maintained in Cornea Syn® and Cornea Trans® did not affect the ECD and functional outcomes of UT-DSAEK up to 12 months.

An increased odontogenic chronic rhinosinusitis (oCRS) occurrence rate has quite recently been reported, likely due to an intensification of conservative dental surgery and implantology. The main aim of the study was to report for the first time the structured histopathological characteristics of the surgical specimens of oCRS. Possible associations between histopathological features and oCRS patho-physiological mechanisms were also evaluated. Structured histopathology features were investigated in the sinonasal mucosa tissue of 42 consecutive oCRS patients.Mean tissue eosinophil counts were significantly different between oCRS with radicular cysts, dental implants, or other dental diseases ( p =0.0118): mean tissue eosinophil count was higher in oCRS with dental implants. Sub-epithelial edema score and squamous metaplasia presence were significantly different when comparing the above-mentioned sub-cohorts of oCRS ( p =0.0099 and p =0.0258). In particular, squamous metaplasia was more present in oCRS cases with radicular cysts than in those with a dental implant ( p =0.0423). Fibrosis presence was significantly different comparing the three sub-cohorts of oCRS ( p =0.0408), too. This preliminary evidence supports the hypothesis that: (i) structural histopathology can become a useful tool for clinic-pathological practice in diagnostic, therapeutic, and prognostic terms in CRS; (ii) that oCRS, as CRS in general, is a histo-pathologically heterogeneous disease; (iii) oCRS resulting from dental implants disorders can frequently be characterized as a CRS with a rich tissue eosinophilic component., Competing Interests: The authors declare no conflicts of interest.

Different cognitive aids have been recently developed to support the management of cardiac arrest, however, their effectiveness remains barely investigated. We aimed to assess whether clinicians using any cognitive aids compared to no or alternative cognitive aids for in-hospital cardiac arrest (IHCA) scenarios achieve improved resuscitation performance. PubMed, EMBASE, the Cochrane Library, CINAHL and ClinicalTrials.gov were systematically searched to identify studies comparing the management of adult/paediatric IHCA simulated scenarios by health professionals using different or no cognitive aids. Our primary outcomes were adherence to guideline recommendations (overall team performance) and time to critical resuscitation actions. Random-effects model meta-analyses were performed. Of the 4.830 screened studies, 16 (14 adult, 2 paediatric) met inclusion criteria. Meta-analyses of eight eligible adult studies indicated that the use of electronic/paper-based cognitive aids, in comparison with no aid, was significantly associated with better overall resuscitation performance [standard mean difference (SMD) 1.16; 95% confidence interval (CI) 0.64; 1.69; I 2  = 79%]. Meta-analyses of the two paediatric studies, showed non-significant improvement of critical actions for resuscitation (adherence to guideline recommended sequence of actions, time to defibrillation, rate of errors in defibrillation, time to start chest compressions), except for significant shorter time to amiodarone administration (SMD - 0.78; 95% CI - 1.39; - 0.18; I 2  = 0). To conclude, the use of cognitive aids appears to have benefits in improving the management of simulated adult IHCA scenarios, with potential positive impact on clinical practice. Further paediatric studies are necessary to better assess the impact of cognitive aids on the management of IHCA scenarios., (© 2022. The Author(s).)

Objectives: The interaction between tumor cells and stroma is critical in tumorigenesis, tumor neo-angiogenesis and cancer progression. The aims of this study were to: (i) evaluate the concordance between tumor-stroma ratio (TSR) and microvascular density (MVD) on paired biopsy and surgical specimens of laryngeal carcinoma (LSCC); (ii) investigate the association of TSR with angiogenesis (CD105- and CD31-assessed MVD); (iii) assess the prognostic role of TSR and MVD evaluated on preoperative biopsies and paired surgical specimens., Methods: TSR, CD105- and CD31-assessed MVD were analyzed in paired biopsies and surgical specimens of 43 consecutive cases., Results: TSR showed good agreement between biopsies and surgical specimens (AC1 statistic: 0.7957). In biopsies, TSR low/stroma-rich cases showed higher CD105-assessed MVD (p = 0.0380). In surgical specimens both median CD105- and CD31-assessed MVD were significantly higher in TSR low/stroma-rich than in TSR high/stroma-poor patients (p = 0.0089 and p = 0.0391). In the univariate Cox's model, TSR predicted disease-free survival (DFS) in both biopsies and surgical specimens (p = 0.0003 and p = 0.0002). DFS was associated with CD105- and CD31-assessed MVD in biopsies (p < 0.0001 for both) and surgical specimens (p < 0.0001 for both). Considering biopsies, the multivariate analysis found both TSR (p = 0.0032; HR = 6.112, 95%CI: 1.833-20.378) and CD105-assessed MVD (p = 0.0002; HR = 1.201, 95%CI: 1.090-1.322) as DFS predictor. In paired surgical specimens, both TSR (p = 0.0074; HR = 6.137, 95%CI: 1.626-23.172) and CD105-assessed MVD (p = 0.0005; HR = 1.172 95 %CI 1.071-1.282) retained their significance in multivariate analysis., Conclusions: If confirmed by large prospective studies, TSR and MVD could be proposed as prognostic biomarkers of LSCC for a possible treatment intensification or targeted therapy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Importance: Pediatric cardiac arrest is a rare emergency with associated high mortality. Its management is challenging and deviations from guidelines can affect clinical outcomes., Objectives: To evaluate the adherence to guideline recommendations in the management of a pediatric cardiac arrest scenario by teams of pediatric residents. Secondarily, the association between the use of the Pediatric Advanced Life Support-2015 (PALS-2015) pocket card, and the teams' adherence to international guidelines, were explored., Design, Settings and Participants: Multicentre observational simulation-based study at three Italian University Hospitals in 2018, including PALS-2015 certified pediatric residents in their 3rd-5th year of residency program, divided in teams of three., Intervention or Exposure: Each team conducted a standard nonshockable pediatric cardiac arrest scenario and independently decided whether to use the PALS-2015 pocket card., Outcome Measure and Analysis: The primary outcome was the overall number and frequency of individual deviations from the PALS-2015 guidelines, measured by the novel c-DEV15plus score (range 0-15). Secondarily, the performance on the validated Clinical Performance Tool for asystole scenarios, the time to perform resuscitation tasks and cardiopulmonary resuscitation (CPR) quality metrics were compared between the teams that used and did not use the PALS-2015 pocket card., Main Results: Twenty-seven teams (81 residents) were included. Overall, the median number of deviations per scenario was 7 out of 15 [interquartile range (IQR), 6-8]. The most frequent deviations were delays in positioning of a CPR board (92.6%), calling for adrenaline (92.6%), calling for help (88.9%) and incorrect/delayed administration of adrenaline (88.9%). The median Clinical Performance Tool score was 9 out of 13 (IQR, 7-10). The comparison between teams that used ( n  = 13) and did not use ( n  = 14) the PALS-2015 pocket card showed only significantly higher Clinical Performance Tool scores in the former group [9 (IQR 9-10) vs. 7 (IQR 6-8); P  = 0.002]., Conclusions: Deviations from guidelines, although measured by means of a nonvalidated tool, were frequent in the management of a pediatric cardiac arrest scenario by pediatric residents. The use of the PALS-2015 pocket card was associated with better Clinical Performance Tool scores but was not associated with less deviations or shorter times to resuscitation tasks., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The 2020 severe acute respiratory syndrome coronavirus 2 outbreak entailed reduced availability of traditional (in-office) cardiology consultations. Remote monitoring is an alternative way of caring that may potentially mitigate the negative effects of the epidemic to the care of cardiovascular diseases. We evaluated the outcome of implantable cardioverter defibrillator (ICD) carriers followed up remotely in 2020 (epidemic period) versus 2019 (control)., Methods: We included all patients with an ICD who remained remotely monitored from the beginning to the end of each year. The combined end point included: new-onset atrial fibrillation; sustained ventricular tachycardia >170 bpm without ICD intervention; appropriate ICD intervention (either shock or antitachycardia pacing); any-cause death. Multiple events in the same patients were counted separately if occurring ≥48 h apart., Results: In 2020, 52 end points occurred in 37 of 366 (10%) ICD carriers [0.14/patient (95% confidence interval [CI] = 0.11-0.19)] versus 43 end points in 32 of 325 (10%) ICD carriers in 2019 [0.13/patient (95% CI = 0.10-0.18) P  = 0.75]. There was no difference between the distribution of any individual end point in 2020 versus 2019 although a nonsignificant mortality increase was observed (from 2.8% to 4.6%, P  = 0.19). The lowest weekly event rate occurred during the national lock down in spring 2020 but a similar trend occurred also in 2019 suggesting that the effect may not be linked to social distancing measures., Conclusions: We did not observe an increase in a combined end point including arrhythmic events and mortality in ICD carriers who were remotely monitored in 2020, compared to 2019, despite the negative impact of the coronavirus disease 2019 outbreak on the healthcare system., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Programmed cell death ligand 1 (PD-L1) seems to rely on close relations between neoplastic and immune cells in the tumor microenvironment. Tumor to stroma ratio (TSR) has been associated with prognosis in different malignancies. The aims of this exploratory investigation were to analyze for the first time the: (i) association between TSR, PD-L1 expression and other clinical−pathological features in laryngeal squamous cell carcinoma (LSCC) biopsies and paired surgical specimens; (ii) prognostic and predictive role of TSR and PD-L1. TSR, PD-L1 expression (in terms of combined positive score [CPS]), and other clinical−pathological features were analyzed in biopsies and surgical specimens of 43 consecutive LSCC cases. A CPS < 1 evaluated on surgical specimens was associated with a low TSR (stroma rich) on both biopsies and surgical specimens (p = 0.0143 and p = 0.0063). Low TSR showed a significant negative prognostic value when evaluated on both biopsies and surgical specimens (HR = 8.808, p = 0.0003 and HR = 11.207, p = 0.0002). CPS ≥ 1 appeared to be a favorable prognostic factor (HR = 0.100, p = 0.0265). The association between bioptic and surgical specimen TSR and PD-L1 expression should be further investigated for a potential impact on targeted treatments, also with regard to immunotherapeutic protocols.

Objectives: Oral lichen planus (OLP) is an inflammatory disease. Bioelectrical impedance analysis (BIA) is a method for assessing tissue composition. Based on a combination of reactance and resistance data, a phase angle is calculated that may range from 90° to 0°, and that correlates with body cell mass. There is evidence to suggest that neoplastic tissue has a lower phase angle than normal tissue. The aim of the present experimental study was to establish whether OLP patients have a different tissue phase angle from healthy controls. Materials and Methods: Bioelectrical impedance measurements were obtained for the buccal mucosa, tongue, hard palate and upper anterior gums using an ad hoc device in a sample of 57 consecutive patients with OLP and 60 healthy controls, and their phase angles were calculated. Results: The mean resistance, reactance, and phase angle of the hard palate and gums were higher in the OLP group than in the controls, and the differences were statically significant. The resistance and reactance recorded for the adherent gingiva and hard palate were always higher in the OLP group (p = 0.044; p = 0.020; p = 0.054), and so was the phase angle for the adherent gingiva. No statistically significant differences emerged for the other areas of the oral cavity (p < 0.05). Conclusion: These findings confirm differences between the bioelectrical impedance of OLP lesions and that of healthy oral tissues. Clinical relevance: Bioelectrical impedance analysis could be useful in the diagnosis of OLP.