The pediatric DAV-expert algorithm: A GAVeCeLT/GAVePed consensus for the choice of the most appropriate venous access device in children.

In pediatric patients, the choice of the venous access device currently relies upon the operator's experience and preference and on the local availability of specific resources and technologies. Though, considering the limited options for venous access in children if compared to adults, such clinical choice has a great critical relevance and should preferably be based on the best available evidence. Though some algorithms have been published over the last 5 years, none of them seems fully satisfactory and useful in clinical practice. Thus, the GAVePed-which is the pediatric interest group of the most important Italian group on venous access, GAVeCeLT-has developed a national consensus about the choice of the venous access device in children. After a systematic review of the available evidence, the panel of the consensus (which included Italian experts with documented competence in this area) has provided structured recommendations answering 10 key questions regarding the choice of venous access both in emergency and in elective situations, both in the hospitalized and in the non-hospitalized child. Only statements reaching a complete agreement were included in the final recommendations. All recommendations were also structured as a simple visual algorithm, so as to be easily translated into clinical practice.

Lung Cancer Screening: The European Perspective.

Several randomized and observational studies on lung cancer screening held in Europe significantly contributed to the knowledge on low-dose computed tomography screening targets in high-risk individuals with smoking history and older than 50 years. In particular, steps forward have been made in the field of risk modeling, screening interval, diagnostic protocol with volumetry, optimization, overdiagnosis estimation, oncological outcome, oncological risk due to radiation exposure, recruitment, and communication strategy.

Prolonged air leak after robotic lung resection: a narrative review.

Background and Objective: Prolonged air leak (PAL) following lung resection is related to an increase in morbidity and both direct and indirect costs. In recent years, robotic-assisted thoracic surgery (RATS) has proved to be a safe technique with comparable perioperative outcomes of video-assisted thoracic surgery (VATS), optimal oncological results, and potential advantages in case of sublobar resection. We here focus on the incidence and clinical impact of PAL in the field of robotic surgery and discuss the therapeutic strategies currently available. Methods: We conducted a search on PubMed/MEDLINE and Scopus database from inception until May 27th 2022 to select the relevant literature published in English exploring the occurrence of PAL following RATS. Key Content and Findings: The implementation of robotic surgery led to a significant reduction in PAL occurrence after pulmonary resection compared to open thoracotomy, while there is still no clear advantage with respect to VATS. However, the enhanced dexterity and improved visualization of the robot seem to particularly valuable in case of sublobar lung resection, especially complex ones. Accurate selection of patients based on the presence of risk factors allows the implementation of intraoperative measures in order to reduce the occurrence of PAL. Conclusions: Robotic lung resection is a safe technique, advantageous compared to traditional open thoracotomy in terms of PAL occurrence reduction and it is a valid alternative to manual VATS. Moreover, with the extension of indications for sublobar resection in the treatment of early stage lung cancer, RATS may prove to be the technique of choice thanks to its intrinsic advantages.

Guidelines of the Italian Association of Pediatric Hematology and Oncology for the management of the central venous access devices in pediatric patients with onco-hematological disease.

INTRODUCTION: Central venous accesses devices (CVADs) have a fundamental importance for diagnostic and therapeutic purposes in pediatric onco-hematological patients. The treatment of pediatric onco-hematological diseases is complex and requires the use of integrated multimodal therapies. Long-lasting and safe central venous access is therefore a cornerstone for any successful treatment. METHODS: The aim of this work is to define pediatric guidelines about the management of CVADs in onco-hematology. A panel of experts belonging to the working groups on Infections and Supportive Therapy, Surgery and Nursing of the Italian Pediatric Hematology Oncology Association (AIEOP) revised the scientific literature systematically, scored the level of evidence and prepared these guidelines. The content of the following guidelines was approved by the Scientific Board of AIEOP. RESULTS AND CONCLUSIONS: Important innovations have been developed recently in the field of CVADs, leading to new insertion methods, new materials and new strategy in the overall management of the device, especially in the adult population. These guidelines recommend how to apply these innovations in the pediatric population, and are directed to all physicians, nurses and health personnel active in the daily management of CVADs. Their aim is to update the knowledge on CVAD and improve the standard of care in pediatric patients with malignancies.

Venoarterial Extracorporeal Membrane Oxygenation Support in Lung Cancer Resection.

Cardiovascular comorbidities often prevent patients with otherwise resectable early-stage lung cancer from undergoing surgery due to prohibitive perioperative risk. Here we describe the intraoperative use of venoarterial (VA) extracorporeal membrane oxygenation in a stage cIIA lung cancer patient with arterial infiltration and severe postischemic dilated cardiomyopathy (ejection fraction, 0.23) undergoing left upper lobectomy with pulmonary artery angioplasty. Providing intraoperative cardiovascular and respiratory function support, venoarterial extracorporeal membrane oxygenation represents a suitable option for patients with heart failure, ensuring an adequate hemodynamic profile and reducing the risk of complications. Thus, these otherwise inoperable patients can be offered a potentially curative surgical resection of the malignancy.

Lung cancer screening: who pays? Who receives? The European perspectives.

Lung cancer is the leading cause of cancer-related death worldwide, and its early detection is critical to achieving a curative treatment and to reducing mortality. Low-dose computed tomography (LDCT) is a highly sensitive technique for detecting noninvasive small lung tumors in high-risk populations. We here analyze the current status of lung cancer screening (LCS) from a European point of view. With economic burden of health care in most European countries resting on the state, it is important to reduce costs of screening and improve its effectiveness. Current cost-effectiveness analyses on LCS have indicated a favorable economic profile. The most recently published analysis reported an incremental cost-effectiveness ratio (ICER) of €3,297 per 1 life-year gained adjusted for the quality of life (QALY) and €2,944 per life-year gained, demonstrating a 90% probability of ICER being below €15,000 and a 98.1% probability of being below €25,000. Different risk models have been used to identify the target population; among these, the PLCOM2012 in particular allows for the selection of the population to be screened with high sensitivity. Risk models should also be employed to define screening intervals, which can reduce the general number of LDCT scans after the baseline round. Future perspectives of screening in a European scenario are related to the will of the policy makers to implement policy on a large scale and to improve the effectiveness of a broad screening of smoking-related disease, including cardiovascular prevention, by measuring coronary calcium score on LDCT. The employment of artificial intelligence (AI) in imaging interpretation, the use of liquid biopsies for the characterization of CT-detected undetermined nodules, and less invasive, personalized surgical treatments, will improve the effectiveness of LCS.

Pain control and functional improvement in patients treated by autologous conditioned serum after failure of platelet rich plasma treatments in knee osteoarthritis.

OBJECTIVE: To assess the efficacy of autologous conditioned serum (ACS) for the treatment of patients with knee osteoarthritis after failure of medical treatments and platelet rich plasma (PRP) injections. BACKGROUND: Knee osteoarthritis is the most common form of arthritis. Prior to prosthetic surgery these patients might benefit from medical treatments, physiotherapy, and in case of their ineffectiveness, from autologous blood component injections. METHODOLOGY: We have treated 30 patients with Kellgren-Lawrence I-III knee osteoarthritis with ACS after failure of standard medical treatments/physiotherapy and platelet rich plasma (PRP) injections for a full cycle, within the previous year from enrollment. RESULTS: ACS administration was performed in all patients with mild side effects and produced prompt (1 month) improvements of VAS and Lequesne scales in 67% of patients and this result persisted at 6 and 12 months. No relationship between the rate of response and Kellgren-Lawrence scale at enrollment was observed whilst responders had a significantly higher amount of interleukin-1 receptor antagonist (IL1-RA) in ACS as compared to nonresponders. CONCLUSION: The present study confirms the efficacy of ACS in pain control and functional recovery of patients with knee osteoarthritis resistant to medical and PRP treatment. These results were obtained in a well-defined cohort of resistant patients and seem to be related with IL1-RA content in injected ACS.

Distal biceps tendon repair and posterior interosseous nerve injury: clinical results and a systematic review of the literature.

Aim To report clinical, functional and radiographic results of oneincision distal biceps tendon repair with Toggle Loc (Zimmer-Biomet, Warsaw, Indiana, USA) at an average 4-year follow-up and to assess posterior interosseous nerve injury complications after reconstruction. Methods We conducted a retrospective review of 58 consecutive distal biceps tendon repairs performed at our department between 2010 and 2018. Disabilities of Arm, Shoulder and Hand (DASH) score, Visual Analogue Scale (VAS) scale and elbow range of motion (ROM) were recorded at each follow-up and an ultrasound examination was also performed to assess the repaired biceps brachii tendon. Results Clinical evaluation showed good and excellent results at medium- and long-term follow-up. A temporary posterior interosseous nerve (PIN) palsy developed in four (6.81%) patients and always resolved in 8 weeks. PIN palsy prevalence is in accordance with the results of the previous studies. Conclusion Distal biceps tendon repair with Toggle Loc is an effective surgical procedure. PIN injury is a relatively rare complication after one-incision anterior repair. Our complication rate did not differ significantly from other studies that have used cortical button fixation, reported in current literature. Our results confirm that accidental injury of PIN may also happen to experienced surgeons and suggest extreme care and an appropriate surgical technique to reduce this iatrogenic risk.

In defense of the use of peripherally inserted central catheters in pediatric patients.

Central venous access devices have revolutioned the care of children affected by malignancies, facilitating management of complex and prolonged infusive therapies, reducing pain and discomfort related to repeated blood samples and indiscriminate venipunctures, thus reducing also psychological stress of both patients and families. In this respect, peripherally inserted central catheters have been disseminated for use, even in pediatric oncology patients, for their many advantages: easy and non-invasive placement with no risk of insertion-related complications, as well as easy removal; reduced need for general anesthesia both for insertion and removal; adequate prolonged performance also for challenging therapies (e.g. stem cell transplantation); and low rate of late complications. Nonetheless, concerns have been recently raised about use of such devices in children with cancer, especially regarding a presumed (but not demonstrated) high risk of catheter-related venous thrombosis. Are we facing a new witch (or peripherally inserted central catheter) hunt? The choice of the central venous access device-particularly in oncologic children-should be based on an evaluation of clinical advantages and risks, as provided by appropriate and scientifically accurate clinical studies.

Distinguishing multiple lung primaries from intra-pulmonary metastases and treatment implications.

INTRODUCTION: The distinction between multiple primary lung cancers and intra-pulmonary metastases has been extensively investigated because of its important clinical and therapeutic implications. AREAS COVERED: Rapidly improving imaging technology and genomic analysis has led to a finer discrimination between multiple primary lung tumors and pulmonary metastases. However, over the past few decades, standardized criteria for the identification of multiple lung tumors have been lacking. Therefore, in 2017 a multidisciplinary international committee composed of the Union for International Cancer Control (UICC), American Joint Committee on Cancer (AJCC) and International Association for the Study of Lung Cancer (IASLC) addressed this problem when drawing up the 8th edition of TMN stage classification, that now represents a specific consensus on this topic. The most advanced diagnostic strategies associated with screening allow for the detection of early stage synchronous lung cancers. EXPERT OPINION: Although diagnostic confirmation relies on pathologic and clinical examination, new molecular analyses help in the discrimination between primary and secondary tumors. The treatment of multiple primary lung tumors remains, whenever possible, a local treatment based on surgical resection, providing the absence of distant or local (lymph node) metastases.

The role of EBUS-TBNA in lung cancer restaging and mutation analysis.

In recent years, several molecules targeting specific genetic aberrations were released for the treatment of patients affected by locally advanced and metastatic non-small cell lung cancer (NSCLC), leading to an improvement in survival. Moreover, inhibitors of PD-1 and PD-L1 immune checkpoints showed to improve survival, and they are now indicated as first-line treatment in selected patients. Hence, the collection of adequate samples for diagnosis, staging, genotyping and immunohistochemical analysis is a fundamental step in NSCLC treatment planning. When feasible, EBUS-TBNA is suggested as the first-choice diagnostic tool by most of the guidelines. Several studies demonstrated that mutation analysis is viable with high levels of accuracy on both cytological and histological samples obtained by EBUS-TBNA. No technical factor (type of needle, number of passes, use of rapid-on-site-examination, material processing, detection method) has been identified as uniquely influencing the diagnostic yield of molecular analysis. EBUS-TBNA demonstrated to be useful for the restaging of patients affected by locally advanced NSCLC who underwent induction chemotherapy or chemo-radiotherapy, as well as in those who show acquired resistance to targeted therapy and immunotherapy. Nevertheless, most authors agree that a high number of false negative results should be expected due to the likely presence of necrosis and fibrosis induced by neoadjuvant treatments. Therefore, in case of EBUS-TBNA negative sample, pathologic confirmation by surgical biopsy is recommended for the planning of definitive treatment. As suggested by a few preliminary experiences, a wide application of next-generation sequencing (NGS) on EBUS-TBNA specimens will lead to the development of better tailored treatments with simultaneous identification of a large number of gene alterations on a single sample at the time of diagnosis.

Isolated tension pneumoperitoneum following endobronchial ultrasound-guided transbronchial needle aspiration complicated by cardiac peri-arrest: A case report.

Transbronchial needle aspiration under endobronchial ultrasound guidance (EBUS-TBNA) is recommended for the diagnosis and staging of lung cancer. Major complications following EBUS-TBNA are uncommon. We report a case of isolated tension pneumoperitoneum following EBUS-TBNA under deep sedation in an 80-year-old male patient affected by a right hilar mass suspicious for lung cancer. At the end of the procedure, the patient suddenly manifested desaturation, severe bradycardia and hypotension, and abdominal distension. After resuscitation, in the suspect of intraperitoneal free air, needle decompression led to respiratory and hemodynamic improvement. A total body CT-scan showed isolated pneumoperitoneum without signs of gastrointestinal perforation, confirmed by a subsequent upper digestive contrast study. The patient recovered well without the need of surgical exploration. Isolated tension pneumoperitoneum can be an exceptional complication of EBUS-TBNA; a conservative treatment can avoid unnecessary surgery in the absence of peritonism.

18F-FAZA PET/CT in the Preoperative Evaluation of NSCLC: Comparison with 18F-FDG and Immunohistochemistry.

PURPOSE: To assess the capability of 18F-FAZA PET/CT in identifying intratumoral hypoxic areas in early and locally advanced non-small cell lung cancer (NSCLC) patients and to compare 18FFAZA PET/CT with 18F-FDG PET/CT and histopathological biomarkers and to investigate whether the assessment of tumour to blood (T/B) and tumour to muscle (T/M) ratios provide comparable information regarding the hypoxic fractions of the tumour. MATERIALS AND METHODS: Seven patients with NSCLC were prospectively enrolled (3 men, 4 women; median age: 71 years; range 63-80). All patients underwent to 18F-FDG PET/CT and 18F-FAZA PET/CT before surgery. Maximum standardized uptake value (SUVmax) was used to evaluate 18FFDG PET/CT images, while 18F-FAZA PET/CT images have been interpreted by using tumour-toblood (T/B) and tumour-to-muscle (T/M) ratio. Surgery was performed in all patients; immunohistochemical analysis for hypoxia biomarkers was performed on histologic tumor samples. RESULTS: All lung lesions showed intense 18F-FDG uptake (mean SUVmax: 7.35; range: 2.35-25.20). A faint 18F-FAZA uptake was observed in 6/7 patients (T/B < 1.2) while significant uptake was present in the remaining 1/7 (T/B and T/M=2.24). On both 2 and 4 h imaging after injection, no differences were observed between T/M and T/B (p=0.5), suggesting that both blood and muscle are equivalent in estimating the background activity for image analysis. Immunohisotchemical analysis showed low or absent staining for hypoxia biomarkers in 3 patients (CA-IX and GLUT-1: 0%; HIF-1α: mean 3.3%; range 0-10). Two patients showed staining for HIF-1α of 5%, with CA-IX being 60% and 30%, respectively and GLUT-1 being 30% and 80%, respectively; in 1/7 HIF-1α was 10%, CA-IX was 50% and GLUT-1 was 90%. In one patient a higher percentage of HIF-1α and CA-IX (20% and 70%, respectively) positive cells was present, with GLUT-1 being 30%. CONCLUSIONS: To the best of our knowledge, this is the first paper assessing hypoxia and glucose metabolism in comparison with immunohistochemistry in patients candidate to surgery for NSCLC. Although including a small number of patients, useful insight regarding correlation between imaging and immunohistochemistry are reported along with methodological suggestions for clinical practice.

Concomitant Lung Cancer and Gastrointestinal Stromal Tumor: First Report of Hypoxia Imaging With 18F-FAZA PET/CT.

A 76-year-old man underwent F-FDG PET/CT to complete staging and characterize a suspicious lung mass. Images showed intense uptake in the lung lesion and faint uptake in correspondence of a gastric mass, which was subsequently biopsied revealing a gastrointestinal stromal tumor. A F-FAZA PET/CT was also performed because of patient's enrollment in a prospective clinical trial (trial registration no. EudraCT 2011-002647-98), showing heterogeneous uptake of F-FAZA in the pulmonary lesion and faint uptake in correspondence of the gastrointestinal stromal tumor.

First Evaluation of PET-Based Human Biodistribution and Dosimetry of 18F-FAZA, a Tracer for Imaging Tumor Hypoxia.

18F-labeled fluoroazomycinarabinoside (18F-FAZA) is a PET biomarker for noninvasive identification of regional tumor hypoxia. The aim of the present phase I study was to evaluate the biodistribution and dosimetry of 18F-FAZA in non-small cell lung cancer patients. Methods: Five patients awaiting surgical resection of histologically proven or radiologically suspected non-small cell lung cancer were prospectively enrolled in the study. The patients underwent PET/CT after injection of 371 ± 32 MBq of 18F-FAZA. The protocol consisted of a 10-min dynamic acquisition of the heart to calculate the activity in blood, followed by 4 whole-body PET/CT scans, from the vertex to the mid thigh, at 10, 60, 120, and 240 min after injection. Urine samples were collected after each imaging session and at 360 min after injection. Volumes of interest were drawn around visually identifiable source organs to generate time-activity curves. Residence times were determined from time-activity curves, and effective doses to individual organs and the whole body were calculated using OLINDA/EXM 1.2 for the standard male and female phantoms. Results: Blood clearance was characterized by a rapid distribution followed by first-order elimination. The highest uptake was in muscle and liver, with respective percentage injected activity (%IA) peaks of 42.7 ± 5.3 %IA and 5.5 ± 0.6 %IA. The total urinary excretion was 15 %IA. The critical organ, with the highest absorbed radiation doses, was the urinary bladder wall, at 0.047 ± 0.008 and 0.067 ± 0.007 mGy/MBq for the 2- and 4-h voiding intervals, respectively. The effective doses for the standard male and female phantoms were 0.013 ± 0.004 and 0.014 ± 0.004 mSv/MBq, respectively, depending on the voiding schedule. Conclusion: With respect to the available literature, the biodistribution of 18F-FAZA in humans appeared to be slightly different from that in mice, with a low clearance in humans. Therefore, use of animal data may moderately underestimate radiation doses to organs in humans. Our dosimetry data showed that a 370-MBq injection of 18F-FAZA is safe for clinical use, similar to other widely used PET ligands. In particular, the effective dose is not appreciably different from those obtained with other hypoxia tracers, such as 18F-fluoromisonidazole.

Determination of Interference During In Vitro Pyrogen Detection: Development and Characterization of a Cell-Based Assay.

Contamination of pharmaceutical products and medical devices with pyrogens such as endotoxins is the most common cause of systemic inflammation and, in worst cases, of septic shock. Thus, quantification of pyrogens is crucial. The limulus amebocyte lysate (LAL)-based assays are the reference tests for in vitro endotoxin detection, in association with the in vivo rabbit pyrogen test (RPT), according to European Pharmacopoeia (EP 2.6.14), and U.S. Pharmacopoeia (USP <85>). However, several substances interfere with LAL assay, while RPT is not accurate, not quantitative, and raises ethical limits. Biological assays, as monocyte activation tests, have been developed and included in European Pharmacopoeia (EP 7.0; 04/2010:20630) guidelines as an alternative to RPT and proved relevant to the febrile reaction in vivo. Because this reaction is carried out by endogenous mediators under the transcriptional control of nuclear factor-kappaB (NF-kappaB), we sought to determine whether a NF-kappaB reporter-gene assay, based on MonoMac-6 (MM6) cells, could reconcile the basic mechanism of innate immune response with the relevance of monocytoid cell lines to the organism reaction to endotoxins. This article describes both optimization and characterization of the reporter cells-based assay, which overall proved the linearity, accuracy, and precision of the test, and demonstrated the sensitivity of the assay to 0.24 EU/mL endotoxin, close to the pyrogenic threshold in humans. Moreover, the assay was experimentally compared to the LAL test in the evaluation of selected interfering samples. The good performance of the MM6 reporter test demonstrates the suitability of this assay to evaluate interfering or false-positive samples.

Hypovitaminosis D3, Leukopenia, and Human Serotonin Transporter Polymorphism in Anorexia Nervosa and Bulimia Nervosa.

Vitamin D3 has been described to have different extraskeletal roles by acting as parahormone in obesity, diabetes, cancer, cognitive impairment, and dementia and to have important regulatory functions in innate immunity. There are no studies showing extraskeletal changes associated with hypovitaminosis D3 in eating disorders. Methods. We have analyzed the blood of 18 patients affected by anorexia nervosa and bulimia nervosa collected over a 15-month period. We performed a panel of chemical and clinical analyses: the assay of vitamin D3, the immunoblotting of vitamin D receptor and peroxisome proliferator-activated receptor gamma, and the genotyping of 5-hydroxytryptamine transporter linked polymorphic region. Results. We choose 18 patients with a normal blood test profile such as thyroid hormones, hepatic and renal parameters, triglycerides, proteins, vitamin B12, and folic acid. Among these emerged the case of a woman with long-term anorexia nervosa and the case of a woman with long-term bulimia nervosa both complicated by anxiety and depression, severe hypovitaminosis D3, decrease of vitamin D receptor, leukopenia, and 5-hydroxytryptamine transporter linked polymorphic region short allele. Conclusion. The results induce hypothesising that the severe hypovitaminosis D3 might be responsible for the lack of the inflammatory response and the depressive symptoms in patients with long-term eating disorders.

The intracavitary ECG method for positioning the tip of central venous access devices in pediatric patients: results of an Italian multicenter study.

PURPOSE: The Italian Group for Venous Access Devices (GAVeCeLT) has carried out a multicenter study investigating the safety and accuracy of intracavitary electrocardiography (IC-ECG) in pediatric patients. METHODS: We enrolled 309 patients (age 1 month-18 years) candidate to different central venous access devices (VAD) - 56 peripherally inserted central catheters (PICC), 178 short term centrally inserted central catheters (CICC), 65 long term VADs, 10 VADs for dialysis - in five Italian Hospitals. Three age groups were considered: A (<4 years, n = 157), B (4-11 years, n = 119), and C (12-18 years, n = 31). IC-ECG was applicable in 307 cases. The increase of the P wave on IC-ECG was detected in all cases but two. The tip of the catheter was positioned at the cavo-atrial junction (CAJ) (i.e., at the maximal height of the P wave on IC-ECG) and the position was checked during the procedure by fluoroscopy or chest x-ray, considering the CAJ at 1-2 cm (group A), 1.5-3 cm (group B), or 2-4 cm (group C) below the carina. RESULTS: There were no complications related to IC-ECG. The overall match between IC-ECG and x-ray was 95.8% (96.2% in group A, 95% in group B, and 96.8% in group C). In 95 cases, the IC-ECG was performed with a dedicated ECG monitor, specifically designed for IC-ECG (Nautilus, Romedex): in this group, the match between IC-ECG and x-ray was 98.8%. CONCLUSIONS: We conclude that the IC-ECG method is safe and accurate in the pediatric patients. The applicability of the method is 99.4% and its feasibility is 99.4%. The accuracy is 95.8% and even higher (98.8%) when using a dedicated ECG monitor.

Thermal modifications of root transparency and implications for aging: a pilot study.

Root transparency has proven to be related to age and has been considered by different odontological methods for age estimation. Very little is known concerning possible variations of root transparency with heat, although the applicability of the method to burnt remains depends on the possible modifications of this specific variable. This pilot study presents the results of an experiment performed on 105 teeth obtained from dental patients and autopsy material, heated in an industrial oven at 50°C, 100°C, 150°C and 200°C. Root transparency was measured before and after the charring experiment. The heating process proved to radically modify root transparency, which decreased in 20% of samples at 50°C, in 34.6% at 100°C, in 50% at 150°C, in 77% at 200°C. The overall correlation index (CI) between decrease in root transparency and increase in temperature amounted to 0.96. These results show that heat may modify root transparency and suggest caution in using methods based on root transparency for age estimation.