Luminescent Behavior of Zn(II) and Mn(II) Halide Derivatives of 4-Phenyldinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepine 4-Oxide and Single-Crystal X-ray Structure Determination of the Ligand.

The two enantiomers of chiral phosphonate 4-phenyldinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepine 4-oxide, O=PPh(BINOL), were synthesized from the proper 1,1'-bi-2-naphtol (BINOL) enantiomer and characterized. The structure of the (S)-enantiomer was elucidated by means of single-crystal X-ray diffraction. The reaction with anhydrous ZnBr2 afforded complexes having the general formula [ZnBr2{O=PPh(BINOL)}2] that showed intense fluorescence centered in the near-UV region rationalized on the basis of TD-DFT calculations. The corresponding Mn(II) complexes with the general formula [MnX2{O=PPh(BINOL)}2] (X = Cl, Br) exhibited dual emission upon excitation with UV light, with the relative intensity of the bands dependent upon the choice of the halide. The highest energy transition is comparable with that of the Zn(II) complex, while the lowest energy emission falls in the red region of the spectrum and is characterized by lifetimes in the hundreds of microseconds range. Although the emission at lower energy can also be achieved by direct excitation of the metal center, the luminescence decay curves suggest that the band in the red range is possibly derived from BINOL-centered excited states populated by intersystem crossing.

From Mono- to Polynuclear 2-(Diphenylphosphino)pyridine-Based Cu(I) and Ag(I) Complexes: Synthesis, Structural Characterization, and DFT Calculations.

A series of monometallic Ag(I) and Cu(I) halide complexes bearing 2-(diphenylphosphino)pyridine (PyrPhos, L) as a ligand were synthesized and spectroscopically characterized. The structure of most of the derivatives was unambiguously established by X-ray diffraction analysis, revealing the formation of mono-, di-, and tetranuclear complexes having general formulas MXL3 (M = Cu, X = Cl, Br; M = Ag, X = Cl, Br, I), Ag2X2L3 (X = Cl, Br), and Ag4X4L4 (X = Cl, Br, I). The Ag(I) species were compared to the corresponding Cu(I) analogues from a structural point of view. The formation of Cu(I)/Ag(I) heterobimetallic complexes MM'X2L3 (M/M' = Cu, Ag; X = Cl, Br, I) was also investigated. The X-ray structure of the bromo-derivatives revealed the formation of two possible MM'Br2L3 complexes with Cu/Ag ratios, respectively, of 7:1 and 1:7. The ratio between Cu and Ag was studied by scanning electron microscopy-energy-dispersive X-ray analysis (SEM-EDX) measurements. The structure of the binuclear homo- and heterometallic derivatives was investigated using density functional theory (DFT) calculations, revealing the tendency of the PyrPhos ligands not to maintain the bridging motif in the presence of Ag(I) as the metal center.

Role of Nasal Nitric Oxide in Primary Ciliary Dyskinesia and Other Respiratory Conditions in Children.

Nitric oxide (NO) is produced within the airways and released with exhalation. Nasal NO (nNO) can be measured in a non-invasive way, with different devices and techniques according to the age and cooperation of the patients. Here, we conducted a narrative review of the literature to examine the relationship between nNO and some respiratory diseases with a particular focus on primary ciliary dyskinesia (PCD). A total of 115 papers were assessed, and 50 were eventually included in the review. nNO in PCD is low (below 77 nL/min), and its measurement has a clear diagnostic value when evaluated in a clinically suggestive phenotype. Many studies have evaluated the role of NO as a molecular mediator as well as the association between nNO values and genotype or ciliary function. As far as other respiratory diseases are concerned, nNO is low in chronic rhinosinusitis and cystic fibrosis, while increased values have been found in allergic rhinitis. Nonetheless, the role in the diagnosis and prognosis of these conditions has not been fully clarified.

Metabolomics Applied to Pediatric Asthma: What Have We Learnt in the Past 10 Years?

Background: Asthma is the most common chronic condition in children. It is a complex non-communicable disease resulting from the interaction of genetic and environmental factors and characterized by heterogeneous underlying molecular mechanisms. Metabolomics, as with the other omic sciences, thanks to the joint use of high-throughput technologies and sophisticated multivariate statistical methods, provides an unbiased approach to study the biochemical-metabolic processes underlying asthma. The aim of this narrative review is the analysis of the metabolomic studies in pediatric asthma published in the past 10 years, focusing on the prediction of asthma development, endotype characterization and pharmaco-metabolomics. Methods: A total of 43 relevant published studies were identified searching the MEDLINE/Pubmed database, using the following terms: "asthma" AND "metabolomics". The following filters were applied: language (English), age of study subjects (0-18 years), and publication date (last 10 years). Results and Conclusions: Several studies were identified within the three areas of interest described in the aim, and some of them likely have the potential to influence our clinical approach in the future. Nonetheless, further studies are needed to validate the findings and to assess the role of the proposed biomarkers as possible diagnostic or prognostic tools to be used in clinical practice.

Standardization of robotic right liver mobilization.

BACKGROUND: Since its introduction 2 decades ago, robotics has been increasingly used for resection of benign and malignant liver lesions. The robotic platform seems to preserve minimally invasive approach benefits, overcoming laparoscopy limitations. Robotic right liver mobilisation represents a key step for many robotic resections from non-anatomical resections of posterosuperior segments to right hepatectomy. METHODS: We present here a standardized technique of right hepatic lobe mobilisation including technical steps and videos. Robotic resection provide all benefits of minimally invasive approaches in terms of preserving abdominal wall, early alimentation, reduced respiratory stress, associated with more ergonomic conditions for surgeon. RESULTS: We present our standardized and feasible right liver lobe mobilisation needed for posterosuperior resections to the right hepatectomy. CONCLUSIONS: The standardisation of right liver lobe represented our aim to provide a safe and reproducible initial step for many procedures to reduce the conversion rate and to improve the learning curve in young surgeons.

Survival benefit of second line therapies for recurrent hepatocellular carcinoma: repeated hepatectomy, thermoablation and second-line transplant referral in a real life national scenario.

BACKGROUND: Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group). METHODS: Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups. RESULTS: 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 - 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 - 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 - 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 - 1.93, p = 0.011). CONCLUSION: It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed.

Robotic emergency liver resection of ruptured hepatocellular carcinoma.

BACKGROUND: The spontaneous rupture of hepatocellular carcinoma (HCC) is a rare complication. The management of this complication needs a stepwise, multidisciplinary approach which considers first of all clinical conditions of the patient and also the possibility of the best curative treatment. METHODS: We report our experience of an emergency robotic liver resection for a ruptured HCC in an elderly patient. Minimally invasive liver resection is currently recognised as a safe and feasible approach to the treatment of HCC in elderly patients. RESULTS: Our patient presented haemodynamic stability, which allows us to perform a robotic resection of segment 3. To our knowledge, this is the first report of the application of a robotic platform in an emergency setting for liver resection. CONCLUSIONS: Rupture of HCC is an uncommon complication, burdened by a high rate of mortality. Its management still remains controversial. Treatment should be individualised taking into consideration the clinical status of the patient, tumour features and possibility of centre therapeutic strategy.

Lung Function in Children with Primary Ciliary Dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is characterized by impaired mucociliary clearance that results in accumulation of mucus and bacteria in the airways. Lower respiratory tract infections lead to airway remodeling and lung function impairment. The aim of our narrative review is to discuss available data on lung function in PCD children, focusing on risk factors for lung function impairment. METHODS: Relevant published studies searching MEDLINE/Pubmed are included in this narrative review, using these terms: "primary ciliary dyskinesia" and "pulmonary function test" or "spirometry" or "lung function". Filters were language (English) and age of study subjects (0-18 years). RESULTS AND CONCLUSIONS: The majority of recent published studies showed normal spirometric values in PCD children, even if some authors described a pulmonary impairment. Together with spirometry, Lung Clearance Index has been applied for detecting peripheral airway disease, and it might have a role in early mild lung disease assessment. Studies on lung function trajectories after PCD diagnosis showed a significant heterogeneity, with some patients maintaining reasonably good lung function, whereas others showing a decline. Further studies are needed to analyze lung function prospectively from childhood into adulthood, and to evaluate whether lung function trajectories are affected by PCD clinical phenotype, ultrastructural ciliary defect or genetic background.

Primary ciliary dyskinesia: A multicenter survey on clinical practice and patient management in Italy.

INTRODUCTION: There are no recent data on primary ciliary dyskinesia (PCD) distribution, diagnosis and treatment in Italy. METHODS: A descriptive study based on a survey questionnaire. It consisted of three sections (patients, diagnosis, and treatment), and sent to all the Italian PCD Centers. RESULTS: Questionnaires obtained from 20/22 centers in 12/20 regions showed that the total number of PCD patients treated at the participating centers was of 416. Out of all centers, 55% follow <20 patients, two centers have >40 patients, and 75% follow both pediatric and adults. Age at diagnosis was between 4 and 8 years in 45% of the centers, <3 years in three centers. Nasal nitric oxide, transmission electron microscopy and ciliary high-speed video microscopy are performed in 75%, 90%, and 40% of centers, respectively. Immunofluorescence is available in five centers. Genetic analysis is offered in 55% of the centers, and in seven centers >50% of the patients have a known genetic profile. Patients treated at all centers receive inhaled saline solutions, corticosteroids and chest physiotherapy. Prophylactic antibiotics and mucolytics are prescribed in 95% and 50% of the centers, respectively. Pseudomonas infection is treated with oral or inhaled antibiotics. CONCLUSIONS: Many Italian centers care for a small number of pediatric and adult patients, and diagnosis is often delayed. We found a great variability in the available diagnostic procedures, as well in the prescribed therapies. Our study will help to uniform diagnostic algorithm and share treatments protocols for PCD in Italy and allowed to set specific national goals.

Hepatocellular Carcinoma with Bile Duct Tumor Thrombus: A Case Report and Literature Review of 890 Patients Affected by Uncommon Primary Liver Tumor Presentation.

Bile duct tumor thrombus (BDTT) is an uncommon finding in hepatocellular carcinoma (HCC), potentially mimicking cholangiocarcinoma (CCA). Recent studies have suggested that HCC with BDTT could represent a prognostic factor. We report the case of a 47-year-old male patient admitted to the University Hospital of Bari with abdominal pain. Blood tests revealed the presence of an untreated hepatitis B virus infection (HBV), with normal liver function and without jaundice. Abdominal ultrasonography revealed a cirrhotic liver with a segmental dilatation of the third bile duct segment, confirmed by a CT scan and liver MRI, which also identified a heterologous mass. No other focal hepatic lesions were identified. A percutaneous ultrasound-guided needle biopsy was then performed, detecting a moderately differentiated HCC. Finally, the patient underwent a third hepatic segmentectomy, and the histopathological analysis confirmed the endobiliary localization of HCC. Subsequently, the patient experienced a nodular recurrence in the fourth hepatic segment, which was treated with ultrasound-guided percutaneous radiofrequency ablation (RFA). This case shows that HCC with BDTT can mimic different types of tumors. It also indicates the value of an early multidisciplinary patient assessment to obtain an accurate diagnosis of HCC with BDTT, which may have prognostic value that has not been recognized until now.

The Effect of a Liver Transplant Program on the Outcomes of Resectable Hepatocellular Carcinoma: A Nationwide Multicenter Analysis.

OBJECTIVE: To evaluate the effect of a liver transplantation (LT) program on the outcomes of resectable hepatocellular carcinoma (HCC). BACKGROUND: Surgical treatment of HCC includes both hepatic resection (HR) and LT. However, the presence of cirrhosis and the possibility of recurrence make the management of this disease complex and probably different according to the presence of a LT program. METHODS: Patients undergoing HR for HCC between January 2005 and December 2019 were identified from a national database of HCC. The main study outcomes were major surgical complications according to the Comprehensive Complication Index, posthepatectomy liver failure (PHLF), 90-day mortality, overall survival, and disease-free survival. Secondary outcomes were salvage liver transplantation (SLT) and postrecurrence survival. RESULTS: A total of 3202 patients were included from 25 hospitals over the study period. Three of 25 (12%) had an LT program. The presence of an LT program within a center was associated with a reduced probability of PHLF (odds ratio=0.38) but not with overall survival and disease-free survival. There was an increased probability of SLT when HR was performed in a transplant hospital (odds ratio=12.05). Among transplant-eligible patients, those who underwent LT had a significantly longer postrecurrence survival. CONCLUSIONS: This study showed that the presence of a LT program was associated with decreased PHLF rates and an increased probability to receive SLT in case of recurrence.

Awake robotic liver surgery: A case report.

BACKGROUND: In recent years, minimally invasive liver resection has become a standard of care for liver tumors. Considering the need to treat increasingly fragile patients, general anesthesia is sometimes avoided due to respiratory complications. Therefore, surgical treatment with curative intent is abandoned in favor of a less invasive and less radical approach. Epidural anesthesia has been shown to reduce respiratory complications, especially in elderly patients with pre-existing lung disease. CASE SUMMARY: A 77-year-old man with hepatitis-C-virus-related chronic liver disease underwent robotic liver resection for hepatocellular carcinoma. The patient was suffering from hypertension, diabetes and chronic obstructive pulmonary disease. The National Surgical Quality Improvement Program score for developing pneumonia was 9.2%. We planned a combined spinal-epidural anesthesia with conscious sedation to avoid general anesthesia. No modification of the standard surgical technique was necessary. Hemodynamics were stable and bleeding was minimal. The postoperative course was uneventful. CONCLUSION: Robotic surgery in locoregional anesthesia with conscious sedation could be considered a safe and suitable approach in specialized centers and in selected patients.

Spending Time with Mothers as a Resource for Children with Chronic Diseases: A Comparison of Asthma, Type 1 Diabetes, and Cancer during COVID-19 Pandemic.

Due to the COVID-19 pandemic, many families had to manage new difficulties, especially those of chronically ill children. More and more research has focused on the negative effects of the pandemic on psychological wellbeing, while less is known about the resources. The present study aimed to explore the role of time spent with mothers in chronically ill children's populations during the COVID-19 pandemic. Moreover, it explored the differences in mothers' and children's psychosocial functioning in three clinical populations. Four groups were recruited and compared: 7-15 year old children with asthma (45), type 1 diabetes (52), and cancer (33), as well as their healthy counterparts (41), and their respective mothers. They were administered standardized questionnaires and ad hoc surveys assessing psychological wellbeing and worries. Children of the four groups scored significantly differently with respect to the concerns for contagion, internalizing symptoms, and prosocial behaviors; mothers had worries about the consequences of their children's contagion related to the chronic illness, as well as time with the child. The multiple linear regression model showed an association of being affected by cancer, suffering from type 1 diabetes, and spending less time with the child with an increase in children's internalizing problems. Time with mothers seemed to be a resource for psychological wellbeing during the pandemic. Clinical implications are discussed.

Percutaneous insertion of a novel dedicated metal stent to treat malignant hilar biliary obstruction.

BACKGROUND: Percutaneous bilateral biliary stenting is an established method for the management of unresectable malignant hilar biliary obstruction. AIM: To evaluate the efficacy and safety of a novel uncovered biliary stent, specifically designed for hilar reconstruction. METHODS: This, single-center, retrospective study included 18 patients (mean age 71 ± 11 years; 61.1% male) undergoing percutaneous transhepatic Moving cell stent (MCS) placement for hilar reconstruction using the stent-in-stent technique for malignant biliary strictures, between November 2020 and July 2021. The Patients were diagnosed with cholangiocarcinoma (12/18; 66.6%), gallbladder cancer (5/18; 27.7%), and colorectal liver metastasis (1/18; 5.5%). Primary endpoints were technical (appropriate stent placement) and clinical (relief from jaundice) success. Secondary endpoints included stent patency, overall survival, complication rates and stent-related complications. RESULTS: The technical and clinical success rates were 100% (18/18 cases). According to Kaplan-Meier analysis, the estimated overall patient survival was 80.5% and 60.4% at 6 and 12 mo respectively, while stent patency was 90.9% and 68.2% at 6 mo and 12 mo respectively. The mean stent patency was 172.53 ± 56.20 d and median stent patency was 165 d (range 83-315). Laboratory tests for cholestasis significantly improved after procedure: mean total bilirubin decreased from 15.2 ± 6.0 mg/dL to 1.3 ± 0.4 mg/dL (P < 0.001); mean γGT decreased from 1389 ± 832 U/L to 114.6 ± 53.5 U/L (P < 0.001). One periprocedural complication was reported. Stent-related complications were observed in 5 patients (27.7%), including 1 occlusion (5.5%) and 1 stent migration (5.5 %). CONCLUSION: Percutaneous hilar bifurcation biliary stenting with the MCS resulted in excellent clinical and technical success rates, with acceptable complication rates. Further studies are needed to confirm these initial positive results.

Impact of COVID-19 in Children with Chronic Lung Diseases.

BACKGROUND: since December 2019, the world has become victim of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The aim of our narrative review is to analyze the impact of COVID-19 in children suffering from chronic lung disease (CLD). METHODS: we searched the MEDLINE/Pubmed database using the terms "SARS-CoV-2" or "COVID-19" or "Coronavirus Diseases 2019"; AND "chronic lung diseases" or "chronic respiratory diseases" or "asthma" or "cystic fibrosis" or "primary ciliary dyskinesia" or "bronchopulmonary dysplasia"; and limiting the search to the age range 0-18 years. RESULTS AND CONCLUSIONS: although COVID-19 rarely presents with a severe course in children, CLD may represent a risk factor; especially when already severe or poorly controlled before SARS-CoV-2 infection. On the other hand, typical features of children with CLD (e.g., the accurate adoption of prevention measures, and, in asthmatic patients, the regular use of inhaled corticosteroids and T2 inflammation) might have a role in preventing SARS-CoV-2 infection. Moreover, from a psychological standpoint, the restrictions associated with the pandemic had a profound impact on children and adolescents with CLD.

Impact of preoperative chemoradiation with higher dose intensity modulated radiotherapy on pathological complete response for locally advanced rectal cancer: a systematic review.

INTRODUCTION: Neoadjuvant chemoradiation (CRT) followed by total mesorectal excision is the current standard-of-care for locally advanced UICC II-III stage rectal cancer (LARC). A pathological complete response (pCR) correlates with survival. Improvements of pCR, including dose escalation, should be explored. The aim of this explorative analysis is to assess the impact on pCR of intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB). AREAS COVERED: A literature search via PICO (Population, Intervention, Comparison, Outcome) in MEDLINE/PubMed and EMBASE and a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Metanalysis) methodology were performed. Studies that reported pCR rate in patients with LARC in clinical stage T2N+M0 or cT3/4 N0/+M0 treated with preoperative CRT with SIB-IMRT/VMAT (Volumetric Modulated Arc Therapy) were included. Sixty-two studies were identified, but only eight clinical trials with a total of 311 patients were included . Median follow-up was 16-61 months. pCR reached the value of 38%. Good survival outcomes were observed with a mild toxicity profile. EXPERT OPINION: Radiotherapy dose intensification in LARC showed a slight increase of pCR compared to historical studies. Prospective evaluations are necessary to define which patients would benefit most.

Impact of air pollution exposure on lung function and exhaled breath biomarkers in children and adolescents.

A growing number of scientific papers focus on the description and quantification of the detrimental effects of pollution exposure on human health. The respiratory system is one of the main targets of these effects and children are potentially a vulnerable population. Many studies analyzed the effects of short- and long-term exposure to air pollutants on children's respiratory function. Aim of the present narrative review is to summarize the results of the available cohort studies which investigated how lung function of children and adolescents is affected by exposure to air pollution. In addition, an overview is provided on the association, in children, between pollution exposure and exhaled breath biomarkers, as possible indicators of the pathogenetic mechanisms involved in pollution-related lung damages. The identified cohort studies suggest that, beside the possible impact of recent exposure, early and lifetime exposure are the variables most consistently associated with a reduction in lung function parameters in both children and adolescents. As for the effect of air pollution exposure on exhaled breath biomarkers, the available studies show an association with increased exhaled nitric oxide, with increased concentrations of malondialdehyde and 8-isoprostane in exhaled breath condensate (EBC), and with EBC acidification. These studies, therefore, suggest lung inflammation and oxidative stress as possible pathogenetic mechanisms involved in pollution related lung damages. Taken together, the available data underscore the importance of the development and application of policies aimed at reducing air pollutant concentration, since the protection of children's lung function can have a beneficial impact on adults' respiratory health in the future.

Preliminary Evidence on Pulmonary Function after Asymptomatic and Mild COVID-19 in Children.

BACKGROUND: While it has been described that adults can develop long-lasting deterioration in pulmonary function (PF) after coronavirus disease 19 (COVID-19), regardless of disease severity, data on the long-term pneumological impact of SARS-CoV-2 infection in children are lacking. METHODS: Performing a single-center, prospective, observational study on children aged 6-18 years with a previous diagnosis of asymptomatic/mild COVID-19, we evaluated the long-term impact of mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children. RESULTS: A total of 61 subjects underwent spirometry after a mean time of 10 ± 4 months from asymptomatic or mild infection. None of the children reported any respiratory symptoms, needed any inhaled therapy, or had abnormal lung function. CONCLUSIONS: In our study, we observed that children and adolescents did not develop chronic respiratory symptoms and did not present lung function impairment after asymptomatic or mild SARS-CoV-2 infection.