Observation of a correlated free four-neutron system.

A long-standing question in nuclear physics is whether chargeless nuclear systems can exist. To our knowledge, only neutron stars represent near-pure neutron systems, where neutrons are squeezed together by the gravitational force to very high densities. The experimental search for isolated multi-neutron systems has been an ongoing quest for several decades1, with a particular focus on the four-neutron system called the tetraneutron, resulting in only a few indications of its existence so far2-4, leaving the tetraneutron an elusive nuclear system for six decades. Here we report on the observation of a resonance-like structure near threshold in the four-neutron system that is consistent with a quasi-bound tetraneutron state existing for a very short time. The measured energy and width of this state provide a key benchmark for our understanding of the nuclear force. The use of an experimental approach based on a knockout reaction at large momentum transfer with a radioactive high-energy 8He beam was key.

Clinical and radiological presentation of parasellar ectopic pituitary adenomas: case series and systematic review of the literature.

PURPOSE: Parasellar ectopic pituitary adenomas (pEPAs) are extremely rare tumors located out of the sella turcica. PEPAs are heterogeneous entities in terms of anatomical localization and secretion of anterior pituitary hormones. METHODS: Multicenter retrospective study. Clinical charts' consultation of patients diagnosed with parasellar lesions, to identify all subjects fulfilling the diagnostic criteria of parasellar EPAs. Systematic review of the literature focused on the medical management of prolactin-secreting pEPAs and on the prevalence of radiological bone invasion in pEPAs. RESULTS: We identified four cases of pEPAs: (1) 54-year-old female with a prolactin-secreting suprasellar EPA successfully treated with cabergoline; (2) 74-year-old male with a non-functioning EPA of the sphenoidal sinus treated with endoscopic transsphenoidal surgery; (3) 75-year-old female with a giant lesion of the skull base (maximum diameter 7.2 cm) diagnosed as a non-functioning EPA after biopsy; (4) 49-year-old male with a silent corticotroph EPA of the sphenoidal sinus and clivus. Three out of four cases had radiological evidence of invasion of the surrounding bone structures. A systematic review of the literature highlighted that medical therapy can be effective in prolactin-secreting pEPAs. Overall, we found mention of local invasiveness in 65/147 cases (44.2%), confirmed by radiological signs of bone invasion/erosion. CONCLUSION: Our experience confirms the heterogeneity of pEPAs in terms of clinical and radiological presentation, as well as hormone secretion. PEPAs show a high frequency of radiological bone invasion, though similar to that of sellar pituitary adenomas. Although extremely rare, pEPAs need to be considered in the differential diagnosis of parasellar lesions.

Probing the Symmetry Energy with the Spectral Pion Ratio.

Many neutron star properties, such as the proton fraction, reflect the symmetry energy contributions to the equation of state that dominate when neutron and proton densities differ strongly. To constrain these contributions at suprasaturation densities, we measure the spectra of charged pions produced by colliding rare isotope tin (Sn) beams with isotopically enriched Sn targets. Using ratios of the charged pion spectra measured at high transverse momenta, we deduce the slope of the symmetry energy to be 42

Identification of N,N-arylalkyl-picolinamide derivatives targeting the RNA-binding protein HuR, by combining biophysical fragment-screening and molecular hybridization.

Hu proteins are members of the RNA-binding protein (RBP) family and play a pivotal role in the regulation of post-transcriptional processes. Through interaction with selected mRNAs, RBPs regulate their function and stability; as a consequence, RBP dysregulation can cause abnormal translation of key proteins involved in several pathologies. In the past few years, this observation has sparked interest to develop new treatments against these pathologies by using small molecules able to modulate RBP activity. Among the four Hu proteins, we have directed our efforts towards the isoform HuR, which is mainly involved in cancer, inflammation and retinopathy. Aimed at developing compounds able to modulate the stability of HuR-mRNA complexes, in the present work, we applied a biophysical fragment screening by assessing a library of halogen-enriched heterocyclic fragments (HEFLibs) via Surface Plasmon Resonance (SPR) and Saturation Transfer Difference (STD) NMR to select promising fragments able to interact with HuR. One selected fragment and a few commercially available congeners were exploited to design and synthesize focused analogues of compound N-(3-chlorobenzyl)-N-(3,5-dihydroxyphenethyl)-4-hydroxybenzamide (1), our previously reported hit. STDNMR spectroscopy, molecular modeling, and SPR offered further insight into the HuR-small molecule interaction and showed that fragment-based approaches represent a promising and yet underexplored strategy to tackle such unusual targets. Lastly, fluorescence polarization (FP) studies revealed the capability of the new compounds to interfere with the formation of the HuR-mRNA complex. This is, to our knowledge, the first fragment-based campaign performed on the Hu protein class, and one of the few examples in the larger RBP field and constitutes an important step in the quest for the rational modulation of RBPs and related RNA functions by small molecules.

Ultra-short antibiotic prophylaxis guided by preoperative microbiological nasal swabs in endoscopic endonasal skull base surgery.

PURPOSE: Endoscopic endonasal skull base surgery (EESBS) is a clean-contaminated procedure. Guidelines regarding the antibiotic prophylaxis in EESBS have not been developed yet, and today, there are no universally accepted protocols. In this article, we investigated the efficacy of our new ultra-short antibiotic prophylaxis protocol for EESBS guided by the cultural results of preoperative microbiological nasal swabs. METHODS: We defined as "nasal swab-related antibiotic protocol" the administration of a first-generation cephalosporin (cefazolin 2 g) in patients whose nasal swabs revealed the presence of normal nasal flora or methicillin-sensitive Staphylococcus aureus (MSSA), and the administration of vancomycin 1 g intravenously in patients whose nasal swabs revealed the presence of methicillin-resistant Staphylococcus aureus (MRSA) or with reported cephalosporin/penicillin allergy. This case-control study included 120 patients who underwent EESBS. The case group included 60 cases who received the "nasal swab-related antibiotic protocol," while the control group included 60 cases who received the "standard hospital antibiotic protocol" used in neurosurgery (cefazolin 2 g plus metronidazole 500 mg at induction, and 2 g of cefazolin repeated after 180 min). RESULTS: The preoperative microbiological nasal swabs showed normal nasal flora in 42 patients (70%), MSSA in 17 patients (28.3%), and MRSA in 1 patient (1.6%). During the study period, no cases of meningitis or sinusitis occurred in the case group ("nasal swab-related antibiotic protocol"), while two infections (3.3%, 1 sinusitis and 1 meningitis) were reported in the control group ("standard hospital antibiotic protocol"). Mean length of hospitalization was 6.5 days for the case group and 8.5 days in the control group. "Standard hospital antibiotic protocol" is less expensive (range, 2.88-5.42 euros) compared with our new "nasal swab-related antibiotic protocol" (range, 10.02-32.56 euros), but in line with other antibiotic prophylaxis protocols reported in literature. DISCUSSION: The low complication rates of our case series (0%) is comparable to complication rates reported in literature (1.6% for meningitis and 8% for sinusitis). Compared with other perioperative antibiotic regimens reported in literature, the "nasal swab-related antibiotic protocol" is cheap and at least equally effective. We discuss the rationale on which we based the choice of chemoprophylaxis, the timing, and the length of our regimen. CONCLUSIONS: Our study confirmed the safety and efficacy of our easily applicable and low-cost antibiotic prophylaxis protocol.

Continuous saline bladder irrigation after blue light transurethral resection of bladder tumor increases recurrence-free survival in low- to intermediate-risk non-muscle invasive bladder cancer.

OBJECTIVES: To evaluate the efficacy of Continuous Saline Bladder Irrigation (CSBI) after blue light transurethral resection of bladder tumor (TURBT) to prevent recurrence of low- to intermediate-risk Non-Muscle Invasive Bladder Cancer (NMIBC). PATIENTS AND METHODS: We conducted a retrospective study including patients with low- to intermediate-risk NMIBC who underwent TURBT in two urological centers between January 2017 and December 2018. Each TURBT was performed using blue light after intravesical instillation of hexaminolaevulinic acid. The experimental group included patients who received CSBI while the control group included patients without CSBI. When practice, CSBI was started immediately after the surgery and was interrupted 24 hours thereafter. Low-risk NMIBC had a surveillance while intermediate NMIBC had 8 adjuvant endovesical instillations of Mitomycin. The primary endpoint was bladder tumor recurrence free-survival which was defined as the time between the initial TURBT and the date of TURBT for bladder recurrence. RESULTS: A total of 167 patients (median age: 71 years) were included: 20% female, 15% low-risk, 85% intermediate-risk NMIBC. CSBI was performed in 95 cases (57%). No complication related to irrigation was reported. Bladder recurrence was observed in 55 cases (32.9%): 22 (23.1%) in the CSBI group vs. 33 (45.8%) in the control group (P=0.002). Multivariate stepwise logistic regression analysis with backward selection revealed that CSBI (HR 0.47 [0.27-0.81]; P=0.006) and MMC (HR 0.55 [0.31-0.95]; P=0.034) were significantly associated with reduced risk of bladder recurrence. CONCLUSIONS: Continuous saline bladder irrigation reduced the risk of bladder recurrence after blue light TURBT in patients with low- to intermediate-risk NMIBC while being safe. Prospective randomized study is needed to confirm these results. LEVEL OF EVIDENCE: 3.

Author Correction: Titanium-carbide MXenes for work function and interface engineering in perovskite solar cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Titanium-carbide MXenes for work function and interface engineering in perovskite solar cells.

To improve the efficiency of perovskite solar cells, careful device design and tailored interface engineering are needed to enhance optoelectronic properties and the charge extraction process at the selective electrodes. Here, we use two-dimensional transition metal carbides (MXene Ti3C2Tx) with various termination groups (Tx) to tune the work function (WF) of the perovskite absorber and the TiO2 electron transport layer (ETL), and to engineer the perovskite/ETL interface. Ultraviolet photoemission spectroscopy measurements and density functional theory calculations show that the addition of Ti3C2Tx to halide perovskite and TiO2 layers permits the tuning of the materials' WFs without affecting other electronic properties. Moreover, the dipole induced by the Ti3C2Tx at the perovskite/ETL interface can be used to change the band alignment between these layers. The combined action of WF tuning and interface engineering can lead to substantial performance improvements in MXene-modified perovskite solar cells, as shown by the 26% increase of power conversion efficiency and hysteresis reduction with respect to reference cells without MXene.

Evidence for a New Compact Symmetric Fission Mode in Light Thorium Isotopes.

Taking benefit of the R3B/SOFIA setup to measure the mass and the nuclear charge of both fission fragments in coincidence with the total prompt-neutron multiplicity, the scission configurations are inferred along the thorium chain, from the asymmetric fission in the heavier isotopes to the symmetric fission in the neutron-deficient thorium. Against all expectations, the symmetric scission in the light thorium isotopes shows a compact configuration, which is in total contrast to what is known in the fission of the heavier thorium isotopes and heavier actinides. This new main symmetric scission mode is characterized by a significant drop in deformation energy of the fission fragments of about 19 MeV, compared to the well-known symmetric scission in the uranium-plutonium region.

Fragmentation of Single-Particle Strength around the Doubly Magic Nucleus

Spectroscopic factors of neutron-hole and proton-hole states in ^{131}Sn and ^{131}In, respectively, were measured using one-nucleon removal reactions from doubly magic ^{132}Sn at relativistic energies. For ^{131}In, a 2910(50)-keV γ ray was observed for the first time and tentatively assigned to a decay from a 5/2^{-} state at 3275(50) keV to the known 1/2^{-} level at 365 keV. The spectroscopic factors determined for this new excited state and three other single-hole states provide first evidence for a strong fragmentation of single-hole strength in ^{131}Sn and ^{131}In. The experimental results are compared to theoretical calculations based on the relativistic particle-vibration coupling model and to experimental information for single-hole states in the stable doubly magic nucleus ^{208}Pb.

New Measures for Research on Men Who Have Sex with Men and for At-Risk Heterosexuals: Tools to Study Links Between Structural Interventions or Large-Scale Social Change and HIV Risk Behaviors, Service Use, and Infection.

Large-scale structural interventions and "Big Events" like revolutions, wars and major disasters can affect HIV transmission by changing the sizes of at-risk populations, making high-risk behaviors more or less likely, or changing contexts in which risk occurs. This paper describes new measures to investigate hypothesized pathways that could connect macro-social changes to subsequent HIV transmission. We developed a "menu" of novel scales and indexes on topics including norms about sex and drug injecting under different conditions, experiencing denial of dignity, agreement with cultural themes about what actions are needed for survival or resistance, solidarity and other issues. We interviewed 298 at-risk heterosexuals and 256 men who have sex with men in New York City about these measures and possible validators for them. Most measures showed evidence of criterion validity (absolute magnitude of Pearson's r ≥ 0.20) and reliability (Cronbach's alpha ≥ 0.70). These measures can be (cautiously) used to understand how macro-changes affect HIV and other risk. Many can also be used to understand risk contexts and dynamics in more normal situations. Additional efforts to improve and to replicate the validation of these measures should be conducted.

Implants outcome inserted in different sites.

Oral rehabilitation by means dental implants has high standards of success. Recently, a new type of two-pieces spiral implants has been introduced in the market. Since few reports focus of the efficacy of this medical device as a reliable tool for oral rehabilitation, here a retrospective study is reported. In the period June-December 2017 one hundred and two spiral fixtures were inserted, half in females and 51 in males. The median age was 56 ± 8 (min-max 36-73 years). Forty-eight implants were inserted in upper jawbone and 54 in mandible. Two implants were lost and thus survival rate (SVR) is 99.9%. Then peri-implant bone resorption was used to investigate the clinical success (success rate, SCR) over time. No implants have a crestal bone resorption greater than 1.5 mm in the first year follow up. No studied variable has an effect on clinical outcome. In conclusion the studied implants have high SCR and SVR so that they are good tools for oral rehabilitation.

Clinical and functional outcomes of cad/cam mandibular reconstruction with free fibular flap comparing traditional versus micro-invasive intraoral surgical approaches.

The surgical incision plays a pivotal role in any surgical procedure. A good surgical approach should allow optimal visualization, respect the anatomy and ensure the best aesthetic outcome possible, especially when the lesions involve the face. In this retrospective study, carried out from June 2014 to April 2018, different types of surgical approaches to perform mandibular reconstruction were compared. Twentyone patients who underwent mandibular reconstruction with free fibular flap (FFFs) using CAD-CAM technology and Virtual Surgical Planning (VSP) were included in the study, regardless the condition, the timing of reconstruction (primary vs secondary), the number of fibular segments or the type and size of the mandibular defect. The patients were treated for mandibular defects secondary to benign or low-grade oncological lesions and different non-oncological conditions. However, patients requiring neck dissection were excluded from the study. Patients were divided into two groups according to the type of surgical approach used: 7 patients received a traditional transcervical approach together with an intraoral approach, while 14 patients were operated through an intraoral approach combined with different microinvasive approaches, including the sub-mandibular, the retro-mandibular and the preauricular approaches. Different factors were statistically compared: characteristics of the harvested fibula, surgical timing, days of hospitalization, as well as complication, functional and aesthetic outcomes. According to this study, no statistically significant differences were observed between the two groups in any of the features considered. These results support the hypothesis that the combination of different microinvasive approaches and the traditional approach are superimposable, and they can be safely exchanged when the underlying defects allow it.

Evaluation of factors influencing accuracy of virtual surgical planning in orthognatic surgery.

Three-dimensional virtual surgical planning has become routine practice in orthognatic and reconstructive surgery for the possibility to realize presurgical evaluation of intraoperative bones movements, the prediction of postoperative results and the high level of accuracy. Thanks to surface superimposition between 3D planned and 3D postoperative model of maxillo-facial skeleton, a medium discrepancy less than 1 mm was found in scientific literature, considering 15 different points of maxillofacial skeleton. In our study we decided to evaluate different factors that could invalidate that result in the same cohort of patients, such as sex, kind of dentofacial deformity, asymmetry, type of surgical approach and entity of maxillo-mandibular movements (more or less than 1 mm). We found out no significant differences among groups. We can state that virtual surgical planning and 3D surgical splints are a valid means of diagnosis, treatment and predictivity regardless factors that could influence post-operative results. In conclusion, virtual surgical planning and 3D surgical splints facilitated diagnosis, treatment planning and accuracy regardless of sex, dentofacial deformity class, surgery techniques, entity of advancement and asymmetry.

Current concepts on cleft lip and palate etiology.

Nonsyndromic cleft lip with or without cleft palate is the most common craniofacial anomaly affecting around 1 in 700 live births worldwide. Clefts of the human face can be classified anatomically as cleft palate only (CPO), cleft lip only (CLO), cleft lip and palate (CLP) or a combined group of cleft lip with or without cleft palate (CL/P), based on different in embryologic development. These malformations have some genetic origin, in fact several association studies have been performed to obtain important information about the candidate genes; but more important are gene-environment interactions that play an increasing role in its etiology. Epidemiological studies have shown how environmental factors (alcohol, smoking, drugs), as well as possible gene-environment interactions, play an important role in the onset of the malformation. On the contrary, folic acid intake seems to have a protective effect. In this review, we analyze the role of environmental factors related to onset of cleft.

Complication in third molar extractions.

Mandibular third molars (MM3s) are responsible for pericoronitis, primary and/or secondary crowding of the dentition, odontogenic tumors and cysts, periodontal defects associated with the posterior part of mandibular second molars. Tooth extraction is indicated for prophylactic and therapeutic purpose in patients with problems caused by impacted teeth. Common postoperative complications associated with third molar extraction are alveolitis (0.5e32.5%), infection (0.9e4.2%), postoperative bleeding (0.2e1.5%), transient dysfunction of the inferior alveolar nerve (0.6e5.5%), and permanent dysfunction of the inferior alveolar nerve (0.1e0.9%). A literature review reveals number of individual case reports of accidental displacement to various anatomical locations, namely, the infratemporal fossa, pterygomandibular space, lateral pharyngeal space, submandibular space, and sublingual space.

[Interest of a systematic assessment of the treatment of the lower urinary tract symptoms in the management of benign prostatic hypertrophy in general practice (1380 patients) - Study EVALURO]. / Intérêt d'une évaluation systématique du traitement des symptômes du bas appareil urinaire dans la prise en charge d'une hypertrophie bénigne de la prostate en médecine générale (1380 patients) ­ Étude EVALURO.

OBJECTIVE: To evaluate the efficacy of a modification or initiation of treatment by a α-blocker in patients already medically treated for BPH-related LUTS, with persistent urinary symptoms. METHODS: This is a prospective observational study among general practitioners in France. Included patients were over 60 years of age with BPH-related LUTS who had been medically treated for at least 6 months. A treatment by an α-blocker was initiated or modified if the PGI-I (Patient Global Impression of Improvement) did not objective any improvement under treatment and the IPSS (International Prostate Symptom Score) was≥8. Patients were followed up between 1 and 3 months after inclusion. The primary endpoint was the frequency of unsatisfactory progression of patients, assessed by persistence of urinary symptoms under treatment (IPSS≥8 and PGI-I unchanged or worsened). Progress of LUTS (IPSS and PGI-I) following modification of treatment with α-blocker was also assessed at the follow-up visit. RESULTS: Three hundred and fifty-three physicians included 1449 patients between February 2, 2016 and March 9, 2017 (1380 patients were analyzed): the average age was 70.0±6.9 years ; the duration of the LUTS was 4.1±4.2 years; at inclusion, they received mainly plants (n=744; 53.9%) and α-blockers (n=463; 33.6%); the mean IPSS score was 16.4±6.7, it was not correlated with duration of SBAU; the mean PGi-I was 2.6±1.2. In total, 48.8% (612/1255) of patients had a non-satisfactory evaluation of the LUTS; 42.8% (591/1380) of patients had a modification of treatment according to the protocol: 385 (65.6%) had an initiation of a α-blocker, 202 (34.4%) had a modification of treatment by α-blocker (4 missing data). The α-blocker was monotherapy for 484 (81.9%) patients. At the follow-up visit (1 to 3 months), the average IPSS score was 7.7±4.8, significantly lower (18.7±6.1 at inclusion); the average PGI-I of 1.2±0.7 was significantly lower (3.5±0.8 at inclusion); the quality of life (Q8-IPSS) was significantly improved. For the 345 patients under plant extracts having changed for one α-blocker, as well as for the 67 patients under α-blocker having changed for another α-blocker, the 3 scores had decreased significantly. CONCLUSION: A systematic evaluation of medical treatment for BPH showed that 48.8% of patients medically treated for at least 6 months were not improved. A modification of treatment by an α-blocker (initiation or modification) can then significantly improve the LUTS.

Genetic landscape of ultra-stable chronic lymphocytic leukemia patients.

Background: Chronic lymphocytic leukemia (CLL) has a heterogeneous clinical course. Beside patients requiring immediate treatment, others show an initial indolent phase followed by progression and others do not progress for decades. The latter two subgroups usually display mutated IGHV genes and a favorable FISH profile. Patients and methods: Patients with absence of disease progression for over 10 years (10-34) from diagnosis were defined as ultra-stable CLL (US-CLL). Forty US-CLL underwent extensive characterization including whole exome sequencing (WES), ultra-deep sequencing and copy number aberration (CNA) analysis to define their unexplored genetic landscape. Microarray analysis, comparing US-CLL with non-US-CLL with similar immunogenetic features (mutated IGHV/favorable FISH), was also carried out to recognize US-CLL at diagnosis. Results: WES was carried out in 20 US-CLL and 84 non-silent somatic mutations in 78 genes were found. When re-tested in a validation cohort of 20 further US-CLL, no recurrent lesion was identified. No clonal mutations of NOTCH1, BIRC3, SF3B1 and TP53 were found, including ATM and other potential progression driving mutations. CNA analysis identified 31 lesions, none with known poor prognostic impact. No novel recurrent lesion was identified: most cases showed no lesions (38%) or an isolated del(13q) (31%). The expression of 6 genes, selected from a gene expression profile analysis by microarray and quantified by droplet digital PCR on a cohort of 79 CLL (58 US-CLL and 21 non-US-CLL), allowed to build a decision-tree capable of recognizing at diagnosis US-CLL patients. Conclusions: The genetic landscape of US-CLL is characterized by the absence of known unfavorable driver mutations/CNA and of novel recurrent genetic lesions. Among CLL patients with favorable immunogenetics, a decision-tree based on the expression of 6 genes may identify at diagnosis patients who are likely to maintain an indolent disease for decades.

The association between extended spectrum beta-lactamase (ESBL) and ampicillin C (AmpC) beta-lactamase genes with multidrug resistance in Escherichia coli isolates recovered from turkeys in Brazil.

1. The aim of this study was to analyse the association between Escherichia coli isolates recovered from turkeys and the expression of beta-lactamase genes, such as extended spectrum beta-lactamase (ESBL) and ampicillin class C (AmpC). The phenotype of the resistance profile was examined using the association between amoxicillin and ceftiofur resistance. 2. Results showed that 84% from the turkey isolates harboured 4 or 5 genes associated with the CoIV plasmid. In an antibiogram test, 82% of the isolates were multidrug-resistant, the highest levels of resistance being against erythromycin (99%) and amoxicillin (76.1%). ESBL-positive groups were 31% positive for the ctx-m-2 gene, 6.8% were positive for ctx-m-8 and 70% harboured the tem wild gene. 3. All positive isolates from the AmpC beta-lactamase-positive group harboured the cmy-2 gene. The presence of the cmy-2 gene was associated with both the CTX-group genes and resistance to ceftiofur. 4. There was a high prevalence of avian pathogenic E. coli in suspected cases of colibacillosis in turkeys and a high antimicrobial resistance index. The results highlighted the risk of ceftiofur resistance and the presence of both ESBL and AmpC beta-lactamase E. coli in the turkey production chain.

Enterocutaneous fistula treatment: case report and review of the literature.

OBJECTIVE: The aim of this work is to evaluate the treatment strategies for a common major surgery complication like the enterocutaneous fistula (ECFs). Since there is not any standard treatment for this common disease and since new therapies, like NPWT and fibrin sealants, have come up a review of all their indications seemed useful. We also present two clinical cases treated in this way. PATIENTS AND METHODS: A research was made in the principle databases such as: "Cochrane", "Pubmed", "Google Scholar" and "Google" using the following Key words "enterocutaneous fistula", "fibrin glue", "VAC", "VAC treatment", "fistula", "conservative treatment", "surgery" and using the MESH Function to search similar key words and expand the research. When two or more article with the same design were encountered (e.g. systematic reviews or case reports etc.) the newest one was chosen as data source. RESULTS: As far as somatostatine and its analogues are concerned, they showed a significant reduction of both time (13.95 vs 20.5 days) and percentage (72% vs 44%) of fistula closure against placebo in 2 meta-analysis. NPWT showed a high success rate between 90% and 100% but longer closure time between 4 weeks and 6 months. Fibrin glues showed heterogeneous results due to the great differencies in fistulas anatomy and treatment technique in the various studies, with 64-100% success rate in closure and a median 11,25 vs 23,25 days against total parenteral nutrition (TPN) alone. CONCLUSIONS: Because of ECFs often come up in patient in bad conditions who are not fitted for surgery and because of their high Mortality and Morbidity, a multimodal approach is necessary. Although TPN is a cornerstone of their treatment, NPWT showed is superiority in reducing fistula output and in some cases leading to fistula closure, nevertheless it often needs long treating time. Fibrin glues often needs complex devices and are nota s good as NPWT in treating the around tissues, but they can be useful when fistulas are only accessible from a little external orifice or they show a complex branched tract; thus they are good when surgery is not possible and the fistula has a mid- or low- output. The lack of prospective randomized studies or meta analysis and systematic review to compare the different methodics makes it impossible to show any evidence of superiority, but the combined application seems reasonable for a tailored treatment.