Observed-to-expected lung-area-to-head-circumference ratio on ultrasound examination vs total fetal lung volume on magnetic resonance imaging in prediction of survival in fetuses with left-sided diaphragmatic hernia.

OBJECTIVE: To assess and compare the value of antenatally determined observed-to-expected (O/E) lung-area-to-head-circumference ratio (LHR) on ultrasound examination vs O/E total fetal lung volume (TFLV) on magnetic resonance imaging (MRI) examination to predict postnatal survival of fetuses with isolated, expectantly managed left-sided congenital diaphragmatic hernia (CDH). METHODS: This was a multicenter retrospective study including all consecutive fetuses with isolated CDH that were managed expectantly in Mannheim, Germany, and in five other European centers, that underwent at least one ultrasound examination for measurement of O/E-LHR and one MRI scan for measurement of O/E-TFLV during pregnancy. All MRI data were centralized, and lung volumes were measured by two experienced operators blinded to the pre- and postnatal data. Multiple logistic regression analyses were performed to examine the effect on survival at hospital discharge of various perinatal variables, including the center of management. In left-sided CDH with intrathoracic herniation of the liver, receiver-operating-characteristics (ROC) curves were constructed separately for cases from Mannheim and the other five European centers and were used to compare O/E-TFLV and O/E-LHR in the prediction of postnatal survival. RESULTS: From Mannheim, 309 patients were included with a median gestational age (GA) at ultrasound examination of 29.6 (range, 19.7-39.1) weeks and median GA at MRI examination of 31.1 (range, 18.0-39.9) weeks. From the other five European centers, 116 patients were included with a median GA at ultrasound examination of 26.7 (range, 20.6-37.6) weeks and median GA at MRI examination of 27.7 (range, 21.3-37.9) weeks. Regression analysis demonstrated that the survival rates at discharge were lower in left-sided CDH (odds ratio (OR), 0.349 (95% CI, 0.133-0.918), P = 0.033) and those with intrathoracic liver (OR, 0.297 (95% CI, 0.141-0.628), P = 0.001), and higher with increasing O/E-TFLV (OR, 1.123 (95% CI, 1.079-1.170), P < 0.001), advanced GA at birth (OR, 1.294 (95% CI, 1.055-1.588), P = 0.013) and when birth occurred in Mannheim (OR, 7.560 (95% CI, 3.368-16.967), P < 0.001). Given the difference in survival rate between Mannheim and the five other European centers, ROC curve comparisons between the two imaging modalities were presented separately. For cases of left-sided CDH with intrathoracic herniation of the liver, pairwise comparison showed no significant difference between the area under the ROC curves for the prediction of postnatal survival between O/E-TFLV and O/E-LHR in Mannheim (mean difference = 0.025, P = 0.610, standard error = 0.050), whereas there was a significant difference in the other European centers studied (mean difference = 0.056, P = 0.033, standard error = 0.056). CONCLUSIONS: In fetuses with left-sided CDH and intrathoracic herniation of the liver, the predictive value for postnatal survival of O/E-TFLV on MRI examination and O/E-LHR on ultrasound examination was similar in one center (Mannheim), but O/E-TFLV had better predictive value compared to O/E-LHR in the five other European centers. Hence, in these five European centers, MRI should be included in the diagnostic process for left-sided CDH. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Total intravenous anesthesia (TIVA) with propofool and remifentanil during operative endoscopy tracheobronchial laser therapy.

Background: The aim of our study was to assess how total intra-venous anaesthesia (TIVA) achieved by propofol and remifentanil continuous infusion could ensure proper success of the endobronchial laser therapy, in optimal conditions for the endoscopist, determining at the same time an adequate hypnosis and a good analgesia. Methods: We studied 50 patients (28M - 22F), ASA class I-IV, mean age 42 ± 32.5 years , subjected to laser endoscopy to repair tracheal stenosis. TIVA was performed in all patients, and spontaneous breathing was maintained. Results: 10.2% of patients experienced episodes of coughing during induction. The depth of the anaesthesia plan, monitored by BIS, was 55 ± 5. The awakening was fast in all patients, with an Aldrete score of 7.71 ± 1.14 at 1 minute and 9.31 ± 1.12 at 10 minutes. Conclusion: The results of this study allow us to state that the continuous infusion of propofol and remifentanil proved to be the gold standard in patients ASA I-II-III undergoing endobronchial laser therapy. The use of TIVA has also allowed to perform endoscopic intervention on patients who suffered from a significant decrease of both cardiac and respiratory functions.

The European Hernia Society Prehabilitation Project: A Systematic Review of Intra-Operative Prevention Strategies for Surgical Site Occurrences in Ventral Hernia Surgery.

Background: Ventral hernia repair is one of the most commonly performed surgical procedures worldwide. To reduce the risk of complications, pre- and intra-operative strategies have received increasing focus in recent years. To assess possible preventive surgical strategies, this European Hernia Society endorsed project was launched. The aim of this review was to evaluate the current literature focusing on pre- and intra-operative strategies for surgical site occurrences (SSO) and specifically surgical site infection (SSI) in ventral hernia repair. Methods: A systematic review was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Databases used were Pubmed and Web of Science. Original retrospective or prospective human adult studies describing at least one intra-operative intervention to reduce SSO after ventral hernia repair were considered eligible. Results: From a total of 4775 results, a total of 18 papers were considered suitable after full text reading. Prehospital chlorhexidine gluconate (CHG) scrub appears to increase the risk of SSO in patients undergoing ventral hernia repair, while there is no association between any type of surgical hat worn and the incidence of postoperative wound events. Intraoperative measures as prophylactic negative pressure therapy, surgical drain placement and the use of quilt sutures seem beneficial for decreasing the incidence of SSO and/or SSI. No positive effect has been shown for antibiotic soaking of a synthetic mesh, nor for the use of fibrin sealants. Conclusion: This review identified a limited amount of literature describing specific preventive measures and techniques during ventral hernia repair. An advantage of prophylactic negative pressure therapy in prevention of SSI was observed, but different tools to decrease SSIs and SSOs continuously further need our full attention to improve patient outcomes and to lower overall costs.

Fracture and migration in right atrium of a permanent venous central access system in a elderly patient: case report and literature review.

Abstract: Catheter dislocation and fracture with migration of central venous lines have been reported in the International literature. Catheter fracture with consequent migration has been observed in 0.5-3.0% and may either be consequent to catheter removal or it can occur spontane-ously. Our case report concerns the migration of a Hickman catheter connected to a venous port to the right atrium in a 61-year old patient. A literature up-to-date has been performed to assess the risk of port-a-cath positioning. The position of catheter tip is considered critical for the risk of migration, that is greater as higher the tip localization respect to the carina. The aim of our study is to underline the critical role of X-ray to visualize the exact location of the catheter tip, regard-less of the approach used for catheter positioning.

Achieving the learning curve in total thyroidectomy: a prospective evaluation on resident's training by CUSUM and KPSS analysis.

INTRODUCTION: Total thyroidectomy (TT) is one of the most common procedures among general and endocrine surgeons worldwide. The conventional approach by neck incision is still the most frequently used, despite the growth of mini-invasive approaches. Controversies exist about the optimal learning curve for resident surgeons approaching this procedure. The aim of this study was to compare TT performed by experienced surgeons and residents in two academic hospitals, to define the correct shape of the specific learning curve. METHODS: Between January 2016 and December 2018 patients undergoing TT in two academic departments were prospectively enrolled. In each department patients were divided into four groups: a reference group (A), consisting of 50 consecutive patients operated on by a senior surgeon, and three other groups (B, C, D) of 50 patients each where thyroidectomy was carried out by three different general surgery residents in their last 3 years of residency, respectively. Data were analysed by CUSUM and KPSS tests in order to compare operative time (OT) and its stabilisation during the learning curve. RESULTS: Data from CUSUM test reported that residents could perform TT with OT similar to the senior surgeon after approximately 25-30 procedures, while the KPSS test showed that residents became more stable after 30 procedures, with no increase in perioperative complications. CONCLUSIONS: This prospective study shows how a specific training in thyroid surgery can be reliable thanks to experienced tutors, and confirmed that the effect of dedicated and programmed training may result in positive outcomes for patients requiring thyroidectomy.

The European Hernia Society Prehabilitation Project: a systematic review of patient prehabilitation prior to ventral hernia surgery.

BACKGROUND: Ventral hernia repair is one of the most commonly performed surgical procedures worldwide. To reduce the risk of complications, patient prehabilitation has received increasing focus in recent years. To assess prehabilitation measures, this European Hernia Society endorsed project was launched. The aim of this systematic review was to evaluate the current literature on patient prehabilitation prior to ventral hernia repair. METHODS: The strategies examined were optimization of renal disease, obesity, nutrition, physical exercise, COPD, diabetes and smoking cessation. For each topic, a separate literature search was conducted, allowing for seven different sub-reviews. RESULTS: A limited amount of well-conducted research studies evaluating prehabilitation prior to ventral hernia surgery was found. The primary findings showed that smoking cessation and weight loss for obese patients led to reduced risks of complications after abdominal wall reconstruction. CONCLUSION: Prehabilitation prior to ventral hernia repair may be widely used; however, the literature supporting its use is limited. Future studies evaluating the impact of prehabilitation before ventral hernia surgery are warranted.

Transversus abdominis release (TAR) for ventral hernia repair: open or robotic? Short-term outcomes from a systematic review with meta-analysis.

PURPOSE: To compare early postoperative outcomes after transversus abdominis release (TAR) for ventral hernia repair with open (oTAR) and robotic (rTAR) approach. METHODS: A systematic search of PubMed/MEDLINE, EMBASE, SCOPUS and Web of Science databases was conducted to identify comparative studies until October 2020. A meta-analysis of postoperative short-term outcomes was performed including complications rate, operative time, length of stay, surgical site infection (SSI), surgical site occurrence (SSO), SSO requiring intervention (SSOPI), systemic complications, readmission, and reoperation rates as measure outcomes. RESULTS: Six retrospective studies were included in the analysis with a total of 831 patients who underwent rTAR (n = 237) and oTAR (n = 594). Robotic TAR was associated with lower risk of complications rate (9.3 vs 20.7%, OR 0.358, 95% CI 0.218-0.589, p < 0.001), lower risk of developing SSO (5.3 vs 11.5%, OR 0.669, 95% CI 0.307-1.458, p = 0.02), lower risk of developing systemic complications (6.3 vs 26.5%, OR 0.208, 95% CI 0.100-0.433, p < 0.001), shorter hospital stay (SMD - 4.409, 95% CI - 6.000 to - 2.818, p < 0.001) but longer operative time (SMD 53.115, 95% CI 30.236-75.993, p < 0.01) compared with oTAR. There was no statistically significant difference in terms of SSI, SSOPI, readmission, and reoperation rates. CONCLUSION: Robotic TAR improves recovery by adding the benefits of minimally invasive procedures when compared to open surgery. Although postoperative complications appear to decrease with a robotic approach, further studies are needed to support the real long-term and cost-effective advantages.

Criticism of learning curve in laparoscopic adrenalectomy: a systematic review.

BACKGROUND: Laparoscopic adrenalectomy (LA) has become the treatment of choice for benign adrenal lesions. Lateral Transperitoneal Laparoscopic Adrenalectomy (LTLA) is considered the gold standard. The number of LTLAs a surgeon must perform, in order to complete his learning curve, is not well defined in Literature. Moreover, the few papers dealing with the learning curve for LTLAs show controversial results and consider different evaluation parameters. METHODS: The systematic review has been carried out according to PRISMA statement. The literature search included PubMed and Scopus database. Hand searching of reference lists of previous review articles and relevant studies was also performed. The search string was "learning curve AND laparoscopic adrenalectomy". RESULTS: A total of 9 papers met the inclusion criteria out of 94 non duplicate citations. The aim of this systematic review is to provide a multidimensional evaluation by bringing into focus evaluation parameters of surgical performance, (operative time, intraoperative complications, conversion rate and blood loss), factors related to patient's pathology (side, size, adrenal pathology) and surgeon-specific properties. CONCLUSIONS: Operative time, intraoperative bleeding, intraoperative complications and conversion rate are the main parameters that have been considered for the achievement of learning curve, and for each there are discrepancies, mainly due to the relative rarity of adrenal tumors, and so for difficulties in obtaining approper analysis that could establish an effective learning curve. So, further evaluations in larger experience are needed.

Learning curve in open inguinal hernia repair: a quality improvement multicentre study about Lichtenstein technique.

PURPOSE: Inguinal hernia repair is one of the most performed procedure all over the world with more than 20 million procedures performed each year. Due to the lack of data in literature about the learning curve of the Lichtenstein procedure, we decided to reproduce a research on learning curves with the same methodology proposed in our previous study about laparoscopic hernia repair. The aim of this multicentre study was to analyse how many cases are required to achieve the learning curve for a Lichtenstein procedure. METHODS: We performed a retrospective analysis of the first 100 Lichtenstein procedures performed by 4 trainees from three different institutions and compared them with the same number of procedures performed by 3 senior surgeons from the same institutions. The data about the achieving of learning curve were evaluated with CUSUM and KPSS test. RESULTS: No differences about biometrical features were found between the seven groups of patients. CUSUM analysis showed that the trainees achieve the learning curve after 37-42 procedures, reaching an operative time similar to that one of the senior surgeons. CONCLUSIONS: In conclusion, we have shown that the number of procedures required to reach the learning curve from the beginning of surgical residency is around 40 hernia repairs. This number, produced in a controlled environment under strict supervision, could be the minimum requirement to start the procedure of accreditation and specialization in hernia surgery and is higher and steeper than previously reported.

Cyclic nucleotide-dependent relaxation in human umbilical vessels.

Umbilical vessels have a low sensitivity to dilate, and this property is speculated to have physiological implications. We aimed to investigate the different relaxing responses of human umbilical arteries (HUAs) and veins (HUVs) to agonists acting through the cAMP and cGMP pathways. Vascular rings were suspended in organ baths for isometric force measurement. Following precontraction with the thromboxane prostanoid (TP) receptor agonist U44069, concentration-response curves to the nitric oxide (NO) donor sodium nitroprusside (SNP), the soluble guanylate cyclase (sGC) stimulator BAY 41-2272, the adenylate cyclase (AC) activator forskolin, the ß-adrenergic receptor agonists isoproterenol (ADRB1), salmeterol (ADRB2), and BRL37344 (ADRB3), and the phosphodiesterase (PDE) inhibitors milrinone (PDE3), rolipram (PDE4), and sildenafil (PDE5) were performed. None of the tested drugs induced a relaxation higher than 30% of the U44069-induced tone. Rings from HUAs and HUVs showed a similar relaxation to forskolin, SNP, PDE inhibitors, and ADRB agonists. BAY 41-2272 was significantly more efficient in relaxing veins than arteries. ADRB agonists evoked weak relaxations (< 20%), which were impaired in endothelium-removed vessels or in the presence of the NO synthase inhibitor L-NAME, sGC inhibitor ODQ. PKA and PKG inhibitors impaired ADBR1-mediated relaxation but did not affect ADRB2-mediated relaxation. ADRB3-mediated relaxation was impaired by PKG inhibition in HUAs and by PKA inhibition in HUVs. Although HUA and HUV rings were relaxed by BRL37344, immunohistochemistry and RT-qPCR analysis showed that, compared to ADRB1 and ADRB2, ADRB3 receptors are weakly or not expressed in umbilical vessels. In conclusion, our study confirmed the low relaxing capacity of HUAs and HUVs from term infants. ADRB-induced relaxation is partially mediated by endothelium-derived NO pathway in human umbilical vessels.

Second jejunal loop adenocarcinoma associated with celiac disease: the first case report.

INTRODUCTION: Jejunal adenocarcinoma is a very rare disease but the frequency of this rare carcinoma is higher in celiac patients. We report the first case report of a second jejunal loop adenocarcinoma associated with celiac disease. PRESENTATION OF CASE: A 47-year-old woman, with a history of celiac disease. Computerized tomographic scans of the abdomen and pelvis demonstrated a severe retroperitoneal lymphoadenopathy, para-aortic, inter-aorto-caval, porto-caval, posterior pancreaticoduodenal space, celiac trunk, lesser gastric curvature, lymph node grouping. The patient underwent digiunal resection and regional lymphadenectomy. Diagnosis was poorly differentiated jejunal adenocarcinoma, infiltrating subserosal adipose tissue, metastasing in five out of eight regional lymph nodes. U.I.C.C. 2017 grading = pT3 pN2 G3 R0; Stage IIIB. DISCUSSION: The jejunum accounts for 11-25% of small bowel adenocarcinoma, that accounts for less than 5% of gastrointestinal cancer, notwithstanding that 90% of the mucosa surface area of the digestive tract is made by small intestine. To the best of our knowledge, this is the first report on a second loop jejunal adenocarcinoma complicating celiac disease. In our study, the diagnosis of cancer was made by computed tomography (CT) of abdomen and the patient was operated. For the diagnosis of small bowel tumour, CT enteroclysis has a sensitivity of 85-95% and a specificity of 90-96%. Complete resection (RO) of the jejunal adenocarcinoma, with regional lymph nodes resection and jejuno-jejunal anastomosis should be performed. CONCLUSION: After curative surgical resections of small bowel adenocarcinoma, adjuvant chemo-therapy has not shown a clear benefit in retrospective studies. Preoperative Chemo-Radio-therapy and careful Imaging Staging are the first steps to planning surgery.

Pooled data analysis of primary ventral (PVH) and incisional hernia (IH) repair is no more acceptable: results of a systematic review and metanalysis of current literature.

PURPOSE: Primary (PVHs) and incisional (IHs) ventral hernias represent a common indication for surgery. Nevertheless, most of the papers presented in literature analyze both types of defect together, thus potentially introducing a bias in the results of interpretation. The purpose of this systematic review and meta-analysis is to highlight the differences between these two entities. METHODS: Methods MEDLINE, Scopus, and Web of Science databases were reviewed to identify studies evaluating the outcomes of both open and laparoscopic repair with mesh of PVHs vs IHs. Search was restricted to English language literature. Risk of bias was assessed with MINORS score. Primary outcome was recurrence, and secondary outcomes were baseline characteristics and intraoperative and postoperative data. Fixed effects model was used unless significant heterogeneity, assessed with the Higgins I square (I2), was encountered. RESULTS: The search resulted in 783 hits, after screening; 11 retrospective trials were selected including 38,727 patients. Mean MINORS of included trials was 15.2 (range 5-21). The estimated pooled proportion difference for recurrence was - 0.09 (- 0.11; - 0.07) between the two groups in favor of the PVH group. On metanalysis, PVHs were smaller in area and diameters, affected younger and less comorbid patients, and were more frequently singular; the operative time and length of stay was quicker. Other complications did not differ significantly. CONCLUSION: Our paper supports the hypothesis that PVH and IH are different conditions with the latter being more challenging to treat. Accordingly, EHS classifications should be adopted systematically as well as pooling data analysis should be no longer performed in clinical trials.

Preservation of left colic artery with lymph node dissection of IMA root during laparoscopic surgery for rectosigmoid cancer. Results of a retrospective analysis.

BACKGROUND: During sigmoid or rectal cancer surgery, dissection of lymph-nodes at the origin of inferior mesenteric artery is mandatory. Nevertheless, ligation of the origin of IMA should compromise blood supply to left colon and affect anastomosis. The aim of this retrospective evaluation is to compare high IMA ligation and low IMA ligation with preservation of LCA and skeletonization of the origin of IMA during laparoscopic colorectal resection. METHODS: All 120 patients included were affected by clinically M-0 sigmoid or rectal cancer. A laparoscopic colorectal resection with low or high ligature of IMA was performed. Low ligation was carried out with lymphadenectomy of the arterial root. Patients were divided in 2 groups according to type of treatment: Group A, high IMA ligation (N=65), Group B, low ligation with lymphadenectomy of IMA root (N=55). RESULTS: Preoperatively 59 patients had stage I, 42 patients had stage II  and 19 patients had stage III tumor. A mean of 20.3 +/- 4.5 lymph nodes were removed in group A patients and 18.9 +/- 9.1 in group B patients, and this difference was not statistically significant. Operative time, intraoperative and postoperative complication rates were not different between the two group. CONCLUSIONS: Low IMA ligation combined with lymph-node dissection at its origin is safe and effective, not time consuming and not associated to increased risk of complications and nerve damage. This technique can be considered as alternative to standard high IMA ligation in selected patients.

Right pneumothorax secondary to colonoscopic perforation: a case.

AIM: The purpose of this study is to determine the anatomical aspects, mechanisms, risk factors and appropriate management of development of pneumothorax during a routine colonoscopy. CLINICAL CASE: We report a case of an accidental bowel wall injury during diagnostic colonoscopic with consequent pneumoperitoneum; this was followed by expansion of gas through diaphragmatic fenestration perhaps congenital, in right pleural cavity causing pneumothorax. DISCUSSION: Rarely, colonic perforation during colonoscopy can occur into the extraperitoneal space, thus leading to the passage and diffusion of air along the fascial planes and large vessels, possibly causing pneumoretroperitoneum, pneumomediastinum, pneumopericardium, pneumothorax, and subcutaneous emphysema. The combination of intraperitoneal and extraperitoneal perforation has also been reported. Pneumothorax following a colonoscopy sigmoid perforation is an extremely rare but severe and often lifethreatening complication. CONCLUSION: If the patient develops dyspnea and pneumoderma during or after this procedure, a chest radiogram or thoracoabdominal CT should be taken for diagnostic purposes. Urgent treatment, starting with chest tube insertion(s) and laparotomy or laparoscopy could be lifesaving.

The impact of automatic devices for capillary blood collection on efficiency and pain response in newborns: A randomized controlled trial.

BACKGROUND: The heel stick is the method of choice in most neonatal units for capillary blood sampling, and it represents the most common event among all painful procedures performed on newborns. The type and design of heel stick device and the clinical procedure to collect a blood sample may have an impact on newborn pain response as well. OBJECTIVE: To compare the pain response and efficiency of different automated devices for capillary blood collection in newborns. DESIGN: Randomized clinical trial. SETTING: Postnatal ward of a tertiary-care university hospital in Italy. PARTICIPANTS: Newborn infants at gestational age ≥34 weeks undergoing the metabolic screening test after the 49th hour of life. METHODS: A total of 762 neonates were recruited and randomized into 6 groups (127 babies in each group) assigned to 6 different capillary blood collection devices (Ames Minilet™ Lancet; Cardinal Health Gentleheel®; Natus Medical NeatNick™; BD Quikheel™ Lancet; Vitrex Steriheel® Baby Lancet; Accriva Diagnostics Tenderfoot®). MAIN OUTCOME MEASURES: The following data were collected and assessed for each of the 6 groups evaluated: a) number of heel sticks, b) pain score according to the Neonatal Infant Pain Scale (NIPS) and c) need to squeeze the heel. RESULTS: The Ames Minilet™ Lancet device was found to perform by far the worst compared to the five device underexamination: it required the highest number of sticks (mean=3.91; 95% CI: 3.46-4.36), evoked the most intense pain (mean=3.98; 95% CI: 3.77-4.20), and most frequently necessitated squeezing the heel (92.9%; 95% CI: 86.9-96.3). The five devices under examination appeared to be similar in terms of the number of sticks required, but differed slightly in NIPS score and in need to squeeze the heel. CONCLUSION: The Accriva Diagnostics Tenderfoot® device demonstrated the greatest efficiency for blood sampling and evoked the least pain. With this device, the metabolic screening test could be performed with a single skin incision in the large majority of infants (98.4%), heel squeezing was limited to only 6.3% of infants, and the NIPS score turns out to be lower than other devices in our study (1.22; 95% CI 1.05-1.39).

EDIN Scale Implemented by Gestational Age for Pain Assessment in Preterms: A Prospective Study.

Background. Chronic neonatal pain can lead to long-term adverse effects on the immature brain. EDIN scale for prolonged pain might not be fully suitable for premature infants. We aimed to test a modified EDIN scale, adding postmenstrual age (PMA) as a sixth item (EDIN6). Methods. In a two-phase prospective study, pain was assessed in all neonates admitted in our NICU. In T1 EDIN was applied; in T2 EDIN6 with additional scores of 2, 1, and 0, respectively, for 25-32, 33-37, and >37 weeks PCA was tested. Scores > 6 suggested pain. The nursing staff was given a questionnaire to evaluate EDIN and EDIN6. Results. A total of 15960 pain assessments were recorded (8693 in T1; 7267 in T2). With EDIN6, cumulative detection of pain almost tripled (117/7267 versus 52/8693, p = 0.001). Main differences were found among less mature categories (50/1472 versus 17/1734, p = 0.001 in PCA 25-32; 26/2606 versus 10/4335, p = 0.001 in PMA 33-37; 41/3189 versus 25/2624, p = 0.26 in PMA > 37). Adequacy of pain assessment in lower PMA was judged "medium-high" in 13,4% of nurses in T1 and 71,4% in T2. Conclusions. EDIN6 may allow improved evaluation of pain in preterm infants.

Polymeric drug delivery micelle-like nanocarriers for pulmonary administration of beclomethasone dipropionate.

In this paper, the potential of novel polymeric micelles as drug delivery systems for Beclomethasone Dipropionate (BDP) administration into the lung is investigated. These nanostructures are obtained starting from α,ß-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA), which was subsequently functionalized with O-(2-aminoethyl)-O'-methylpolyethylenglycole (PEG2000), ethylenediamine (EDA) and lipoic acid (LA), obtaining PHEA-PEG2000-EDA-LA graft copolymer. Empty and drug-loaded micelles possess adequate chemical-physical characteristics for pulmonary administration such as spherical shape, slightly positive surface charge and mean size of about 200nm. Besides, BDP-loaded micelles, obtained with a Drug Loading equal to 5wt%, result to be stable in physiological-mimicking media, protecting the drug from hydrolysis and giving a sustained drug release profile. Moreover, the micelle-like structure and surface characteristics seems to improve drug permeation through the mucus layer. Finally, it is also demonstrated that BDP-loaded PHEA-PEG2000-EDA-LA micelles are able to increase cell uptake of BDP of about 44wt% compared to Clenil® on 16-HBE cells and possess an higher biocompatibility in comparison with the same commercial formulation.

Smart Inulin-Based Polycationic Nanodevices for siRNA Delivery.

The advances of short interfering RNA (siRNA) mediated therapy provide a powerful option for the treatment of many diseases by silencing the expression of targeted genes including cancer development and progression. Inulin is a very simple and biocompatible polysaccharide proposed by our groups to produce interesting delivery systems for Nucleic Acid Based Drugs (NABDs), such as siRNA, either as polycations able to give polyplexes and polymeric coatings for nanosystems having a metallic core. In this research field, different functionalizing groups were linked to the inulin backbone with specific aims including oligoamine such as Ethylendiammine (EDA), Diethylediamine (DETA), Spermine, (SPM) etc. In this contribution the main Inulin-based nanodevices for the delivery of siRNA have been reported, analysed and compared with particular reference to their chemical design and structure, biocompatibility, siRNA complexing ability, silencing ability.