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We have read with great interest the paper by Kesić, V. et al. entitled "Early Diagnostics of Vulvar Intraepithelial Neoplasia" [...].

ANITA platform aims at improving investigation capabilities of law enforcement agencies (LEAs) by delivering a set of tools and techniques to efficiently address online illegal trafficking of counterfeit/falsified medicines, novel psychoactive substances (NPS), drugs, and weapons with Artificial Intelligence (AI). Expert.ai has developed a dedicated written content analysis engine to support investigative activity. The market already offers several solutions adopting AI and in particular Machine Learning (ML) to support investigative activities. The particularity of the work carried out in the ANITA project is to adopt a lateral thinking approach and the supervised generation of knowledge from the analysed contents. Rather than focusing on searching for specific proper names of substances, weapons, NPS, etc. that are constantly evolving in considerable speed, we propose to concentrate on searching for precursors, namely collateral concepts related with the target of the investigation. Is the case of accessories for weapons such as sights for rifles or glass vessels used to produce the drugs themselves? This approach is not compatible with the use of ML, but the use of deep semantic analysis of the text is necessary. This article reports the system's ability to automatically identify precursors and generate stimuli and knowledge which the investigator must validate; that enhances the creative and intuitive approach (serendipity) to investigation combining the best of the detective's skills with the power of AI and in particular Natural Language Understanding (NLU).

Summary Background Atypical Spitz tumours (ASTs) are regarded as an intermediate category distinguished from prototypical Spitz naevus by presenting one or more atypical features and often by an uncertain malignant potential. Clinical and dermoscopic features may play a relevant role in the diagnostic approach. Aim To evaluate the clinical and dermoscopic features of ASTs, and their evolution over time. Methods This was a descriptive, multicentre study of the clinical and dermoscopic characteristics of ASTs. Data on clinical and dermoscopic characteristics, histopathology, local extension, therapy and follow-up, lymph node staging, complete lymph node dissection, and outcome were collected from the databases of four Italian Dermatology Units for the period 2004–2021. Results The study population consisted of 99 patients (62 female, 37 male) with a histologically confirmed diagnosis of AST, including age at presentation ranged from 2 to 70 years (mean 28.1 years, median 24 years). Of the 99 patients, 29 (29.3%) underwent sentinel lymph node biopsy, which showed evidence of micrometastases in three cases (10.3%); all three patients underwent complete lymph node dissection with no evidence of further metastasis. Considering the whole study population, the clinical outcome was excellent, as all of the patients have no evidence of recurrence or distant metastasis. The follow-up period ranged from 6 to 216 months (mean 81.6 months, median 78 months). In addition, we collected data on the clinical and dermoscopic features of 26 lesions. The most frequent dermoscopic pattern observed was the multicomponent pattern (34.6%), followed by homogeneous (26.9%) and nonspecific (23.2%). In 66.7% of amelanotic ASTs, we observed glomerular (coiled) vessels uniformly distributed within the entire lesion, without asymmetry. Conclusion The results of our study with a long follow-up show no recurrence or distant metastases, confirming the good clinical outcome, even in the case of sentinel lymph node positivity. From a diagnostic point of view, our series identified a typical dermoscopic picture for amelanotic ASTs, with a glomerular vascular pattern throughout the lesion in the absence of other dermoscopic parameters, making the correct diagnosis possible.

The use of new prosthetic materials makes it necessary to establish adequate hygienic protocols. It was decided to make prosthetic crowns from four different materials: composite, lithium disilicate, metal ceramic, and zirconium, and to evaluate the effects on the surfaces of four different instruments through SEM and roughness analysis: manual steel curette, manual titanium curette, ultrasonic steel insert, and ultrasonic peek insert. Forty crowns were made, ten of each type of material. For each material, five crowns were manually instrumented with steel inserts (curette 11-12, PDT, Missoula, MT, USA) and titanium (Wingrove 3-4, PDT, Missoula, MT, USA) on the lingual and buccal surfaces, respectively, and the other five crowns were instrumented with an ultrasonic peek insert (ICS-IC1, Mectron, Carasco, Italy) on the buccal surface and steel (PS, EMS, Nyon, Switzerland) on the lingual surface. At this point, surface roughness analysis was carried out. The data were analyzed with a Kolmogorov–Smirnov test. Therefore, it was decided to conduct two analyses with a Kruskal–Wallis test and Bonferroni post hoc test. Then, the instrumented crowns were analyzed by SEM. The analysis of the data shows that the highest average roughness was within the composite group, while the best material appeared to be disilicate. Significant differences existed between the groups, between the materials, and between the different instruments (p-value < 0.05). In the qualitative analysis carried out by SEM, the classic steel insert eliminated the residues of golden finishing. The peek insert created alterations on all tested surfaces. The steel curette did not create particular problems, with the exception of zirconium, where it was possible to observe some scratch lines. Instrumentation with the titanium curette created deeper incisions than the steel curette in the composite and disilicate. The best results came from the ultrasonic steel insert, while the best material appeared to be disilicate.

Retroperitoneal soft tissue sarcomas (RPSs) are mesenchymal neoplasms. The prevalence of protein energetic malnutrition (PEM) and its impact in RPS patients who were candidates for surgery is unknown. A prospective feasibility study enrolled 35 patients with primary RPS who were candidates for extended multivisceral resection. PEM was screened at enrollment. Preoperative high protein β-hydroxy-β-methyl butyrate oral nutritional support (ONS) was provided according to the degree of PEM. After surgery, nutritional support followed standard practice, targeting at least 1 g/kg/day protein and 20 kcal/kg/day caloric intake within the third postoperative day (POD). PEM was re-evaluated before surgery on POD 10, and at 4 and 12 months after surgery. Primary outcomes were the patient’s compliance to preoperative ONS and the physician’s compliance to postoperative nutritional targets. PEM was documented in 46% of patients at baseline; ONS met a 91% adherence (overall well tolerated). After ONS, PEM reduced to 38% (p = 0.45). The postoperative caloric target was reached on day 4.1 (standard error ± 2.7), with a protocol adherence rate of 52%. On POD 10, 91% of patients experienced PEM, the worsening of which was greater after resection of four or more organs (p = 0.06). At 4 and 12 months after surgery, almost all patients had fully recovered. A significant correlation between PEM at surgery and postoperative complications was found (p = 0.04). Relevant PEM prevalence in RPS is documented for the first time. PEM correlates with greater morbidity. In this setting, preoperative ONS was feasible and well-tolerated. Disease-related factors for PEM and the ideal perioperative caloric target in the context of extended multivisceral resection need to be further investigated. Nutritional support should be included in enhanced recovery after surgery programs for RPS. ClinicalTrials.gov identifier: NCT03877588.

Objective: Pediatric oncology patients are more likely to develop venous thromboembolic events related to central venous catheter (CVC). Study aim was to determine the incidence of catheter related thrombosis (CRT) in a cohort of pediatric oncology patients using vascular ultrasound (US). Methods: Consecutive children of a single cancer referral center, requiring medium to long term CVC implantation, were screened for CRT, using serial ultrasound exams. Measurements and main results: US examinations were taken 15, 30 and 90 days after CVC implantation. A total of 113 catheters were studied in 103 patients (median age 10.5 years old). Ultrasound screening was completed in 80.5% patients. Apart from three subjects, US investigations were well tolerated. Patients were followed for a median of 87 days. No symptomatic CRT was recorded throughout. Three cases of asymptomatic thrombosis were identified with early US screening; incidence of CRT events for 1000 catheter-days was 0.11. The presence of previous catheter-related infection and an history of one or more previous CVC placement were identified as risk factors. Conclusions: In our pediatric patients the incidence of CRT is low. Ultrasound monitoring is well tolerated and allows detecting asymptomatic CRT. Patients with previous CVC infection or insertion seem to have a higher risk of CRT (p =0.003 and p = 0.043 respectively). Keywords: Central venous catheters, Venous thrombosis, Vascular ultrasound, Vascular catheter infections, Children

Background Recent studies showed that plasma SARS-CoV-2 RNA seems to be associated with worse COVID-19 outcome. However, whether specific population can be at higher risk of viremia are to date unexplored. Methods This cross-sectional proof-of-concept study included 41 SARS-CoV-2-positive adult individuals (six affected by haematological malignancies) hospitalized at two major hospital in Milan, for those demographic, clinical and laboratory data were available. SARS-CoV-2 load was quantified by ddPCR in paired plasma and respiratory samples. To assess significant differences between patients with and patients without viremia, Fisher exact test and Wilcoxon test were used for categorical and continuous variables, respectively. Results Plasma SARS-CoV-2 RNA was found in 8 patients (19.5%), with a median (IQR) value of 694 (209–1023) copies/mL. Viremic patients were characterized by an higher mortality rate (50.0% vs 9.1%; p = 0.018) respect to patients without viremia. Viremic patients were more frequently affected by haematological malignancies (62.5% vs. 3.0%; p p = 0.002). Conclusions Even if based on a small sample population, this proof-of-concept study poses the basis for an early identification of patients at higher risk of SARS-CoV-2 viremia, and therefore likely to develop severe COVID-19, and supports the need of a quantitative viral load determination in blood and respiratory samples of haematologic patients with COVID-19 in order to predict prognosis and consequently to help their further management.

Background. A new instrumentation exploiting magneto-dynamic technology (mallet) proposed for implant site preparation was investigated. Methods. In the tibias of three minipigs, two sites were prepared by mallet and two by drill technique. Primary stability (ISQ) was detected after implant positioning (T0) and at 14 days (T14). X-rays and computed tomography were performed. At T14, bone samples were utilized for histological and biomolecular analyses. Results. In mallet sites, histological evaluations evidenced a significant increase in the newly formed bone, osteoblast number, and a smaller quantity of fibrous tissue. These results agree with the significant BMP-4 augmentation and the positive trend in other osteogenic factors (biological and radiological investigations). Major, albeit IL-10-controlled, inflammation was present. For both techniques, at T14 a significant ISQ increase was evidenced, but no significant difference was observed at T0 and T14 between the mallet and drill techniques. In mallet sites, lateral bone condensation was observed on computed tomography. Conclusions. Using biological, histological, clinical, and radiological analyses, this study first shows that the mallet technique is effective for implant site preparation. Based on its ability to cause osseocondensation and improve newly formed bone, mallet technology should be chosen in all clinical cases of poor bone quality.

Swings of central venous pressure (ΔCVP) may reflect those of pleural and esophageal (ΔPES) pressure and, therefore, the strength of inspiration. Strong inspiratory efforts can produce some harm. Herein we preliminarily assessed the diagnostic accuracy of ΔCVP for strong inspiratory efforts in critically-ill subjects breathing spontaneously.We measured ΔCVP and ΔPES in 48 critically-ill subjects breathing spontaneously with zero end-expiratory pressure (ZEEP) or 10 cmHinf2/infO of continuous positive airway pressure (CPAP). The overall diagnostic accuracy of ΔCVP for strong inspiratory efforts (arbitrarily defined as ΔPES8 mmHg) was described as the area under the receiver operating characteristic (ROC) curve, with 0.50 indicating random guess. The agreement between ΔCVP and ΔPES was assessed with the Bland-Altman analysis.ΔCVP recognized strong inspiratory efforts with an area under the ROC curve of 0.95 (95% confidence intervals, 0.85-0.99) with ZEEP and 0.89 (0.76-0.96) with CPAP, both significantly larger than 0.50 (P0.001). With the best cut-off value around 8 mmHg, the diagnostic accuracy of ΔCVP was 0.92 (0.80-0.98) with ZEEP and 0.94 (0.83-0.99) with CPAP. With ZEEP, the median difference between ΔCVP and ΔPES (bias) was -0.2 mmHg, and the 95% limits of agreement (LoA) were -3.9 and +5.5 mmHg. With CPAP, bias was -0.1 mmHg, and 95%-LoA were -5.8 and +4.5 mmHg. In both cases, ΔCVP correlated with ΔPES (rinfs/inf0.81 and 0.67; P0.001 for both).In critically-ill subjects breathing spontaneously, ΔCVP recognized strong inspiratory efforts with acceptable accuracy. Even so, it sometimes largely differed from ∆PES.

Background Bronchiolitis is the most frequent lower airway infection leading hospitalization in children younger than 2 years. RSV is the typical common cause, followed by rhinovirus. Criteria for Pediatric Intensive Care Unit (PICU) admission are not defined by guidelines. Methods A retrospective analysis of children with severe bronchiolitis admitted from 2013 to 2016 to our PICU was performed to to identify the risk factors associated with intubation in this population. Fourteen variables were studied: sex, weight, age, nationality, provenience, duration of symptoms, risk factors for bronchiolitis development, recurrence, apnea, SpO2 in air, Modified Wood's Clinical Asthma score (M-WCAS), microbiological results, medical treatment, CPAP therapy. The relationship between these variables and the need for mechanical ventilation were explored using univariate and multivariate logistic regression analysis. A ROC analysis was used to identify cut-off for the continuous variables identified as risk factors for intubation in multivariate analysis. Results We enrolled 93 patients, 19 (20.4%) were intubated. Univariate and multivariate analysis demonstrated that a M-WCAS score ≥ 7, SpO2 ≤ 75% and apnea were significantly associated to intubation in children with severe bronchiolitis. Conclusions Cut-off values of the variables identified as risk factors for intubation may represent an important tool for pediatricians to decide a prompt and appropriate intensive respiratory support.

Background Evidence shows lower chance for osseointegration of implants without sufficient primary stability. The present retrospective study observed bone level conical screw implants with textured surface without primary stability. Methods Twenty-six Stark conical screw implants, with V-Blast (Vanish Blast) surface treatment were placed with low primary stability, (insertion torque lower than 10 N/cm and visible mobility at lateral load of 250 g). A soft diet was prescribed. osseointegration was assessed applying 30 Ncm of reverse torque 6 months after placement. Results The 26 implants that did not achieve primary stability still had a survival rate of 96% after the observation period and were classified as successful according with ICOI Pisa consensus conference success, survival, failure classification .96% of the implants showed clinical osteointegration and were successfully restored. After 12 months, all implants remained functional. Conclusions It can be concluded that bone-level implants with V-Blast surface in absence of functional loading are able to achieve osteointegration, even with low primary stability.

Objectives: Rapid and reliable exclusion of invasive fungal infections (IFI) by markers able to avoid unnecessary empirical antifungal treatment is still a critical unmet clinical need. We investigated the diagnostic performance of a newly available β-d-Glucan (BDG) quantification assay, focusing on the optimisation of the BDG cut-off values for IFI exclusion. Methods: BDG results by Wako β-glucan assay (lower limit of detection [LLOD]=2.16pg/mL, positivity≥11pg/mL) on two consecutive serum samples were retrospectively analysed in 170 patients, admitted to haematological wards (N=42), intensive care units (ICUs; N=80), or other wards (N=48), exhibiting clinical signs and/or symptoms suspected for IFI. Only patients with proven IFI (EORTC/MSG criteria) were considered as true positives in the assessment of BDG sensitivity, specificity and predictive values. Results: Patients were diagnosed with no IFI (69.4%), proven IFI (25.3%) or probable IFI (5.3%). Two consecutive BDG values7.7pg/mL, could be a promising diagnostic approach to confidently rule out an IFI in both ICU and non-ICU patients. The poor specificity in the ICU setting remains a concern, due to the difficulty to interpret positive results in this fragile population.

BACKGROUND The purpose of this study was to analyze pulpal temperature increase generated by prosthodontic margin repositioning and finishing with ultrasonic and rotating instruments. The temperature changes recorded were also correlated with the residual dentin thickness. METHODS A sample of 32 human extracted molars was selected. The teeth were endodontically treated and prepared with prosthetic round chamfer preparation. Then, they were inserted in plaster cubes up to the cement-enamel junction, leaving the apical portion pervious for inserting the thermocouple probe. The conventional technique, which involves the use of a high-speed contra-angle handpiece, was compared with an ultrasonic method (Crown Prep, Mectron, Carasco, Italy). For margin repositioning and finishing, two walls were randomly selected for each tooth: one was included in the test group and cut with the piezoelectric instrument (Multipiezo Touch TipHolder DB2, Mectron, Carasco, Genoa, Italy), the other one was inserted in the control group and cut with the high speed contra-angle handpiece (Kavo, Biberach, Germany). To standardize the operator-dependent parameters, it was used a mechanical arm controlled by a computer. These parameters were the pressure exerted on the dental wall, the cutting length and the time required for margin repositioning and finishing. For both test and control group, test phase consisted in a first stage of margin repositioning using an ultrasound tip or a diamond bur with a greater granulometry (120 µm for the ultrasound tip and 125 µm for the diamond bur), followed by a second finishing step conducted by an ultrasound tip or a diamond bur with smaller granulometry (60 µm for the ultrasound tip and 30 µm for the diamond bur). During these stages the intrapulpal temperature was recorded thanks to a thermocouple. Before and after these steps, the thickness of the remaining dental walls was measured with a caliber. RESULTS The average pulpal temperature increase was 5.03±0.98 °C for the ultrasonic preparation (test group) and 3.55±0.95 °C for the conventional technique (control group). The difference was statistically significant (P value

Replacing a single tooth in the anterior maxilla is one of the greatest challenges in dentistry. Both functional and aesthetic results are to be strictly pursued. Planning and executing such a case through a totally digital methodology eventually guarantee many advantages, above all patient’s operative and postoperative comfort. To ascertain this, a BOP analysis was performed which allowed us to evaluate soft tissues health, and more; crestal bone resorption was measured to evaluate hard tissues stability. This assumption was studied through four cases in which patients were alternatively treated with analogic and digital techniques. Four homogeneous patients were recruited. They all needed to extract one of the upper incisors, due to different clinical reasons, and then to replace it with an implant. Each patient was treated with an immediate postextractive implant which was immediately loaded, and finally, analogical and digital techniques were compared. All patients underwent a preoperative CBCT examination. After surgery, patients were checked by the surgeon after 10 days and one month to evaluate the progress of healing and to exclude any prosthetic problem. At 6 months (T1), one year (T2), and three years (T3), intraoral x-rays were performed using customized centring devices, according to the parallel beam technique. All data have been collected in a table and statistically processed; mean and standard deviation were measured. All patients entered an oral hygiene program with six months recall. Dental hygienist checked the BOP at T1, T2, and T3. At every step, similar levels of BOP were recorded. About interproximal bone loss, all patients showed an initial moderate loss (between T1 and T2), followed by stable values between T2 and T3. Despite the important limitations of a study with few cases, these results show a similar outcome comparing digital and analogical methods.

Background Replacement of missing teeth in the anterior aesthetic zone has challenged clinicians with fixed, removable or implant prosthodontics. Problems have been encountered could void aesthetic and functional results. The aim of this study was to present a clinical case report in which clinician challenged a very strong aesthetic case with an innovative surgical and prosthetic approach. Methods A patient who presented to the authors with a maxillary central incisor that had a hopeless prognosis secondary to acute localized severe periodontitis. The patient was treated by extracting the tooth and replacing it immediately with a platform switched implant using piezoelectric surgery. The implant was then restored with an immediate, non-occlusal loading provisional restoration. Results The implant became osseointegrated and was ultimately restored with a definitive abutment and crown restoration. Conclusions Innovative approaches could represent a valid alternative to restore patients functionally and aesthetically.

Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. Here we evaluated the performance of a ddPCR-based assay to quantify SARS-CoV-2 titer in 55 suspected COVID-19 cases with negative rtPCR results thanks to in-house ddPCR assay (targeting RdRp and host RNaseP). Samples were collected at ASST-GOM Niguarda between February and May 2020 at hospital admission. Clinical and imaging data were obtained for clinical staging and definition of disease severity. Patients were mainly female (45.5%) with a median age of 73 (57–84) years. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72–345). In 15 of them (78.9%), chest CT showed a classical COVID-19 bilateral interstitial pneumonia; 14 patients (73.7%) showed severe COVID-19 manifestations. ddPCR did not identify any trace of SARS-CoV-2 genome in the respiratory samples of the remaining 36 patients. The serological assay performed in a subgroup of 34 patients at the later stage of illness (from 3 days to 90 days after) confirmed the presence of SARS-CoV-2 antibodies in all patients tested positive for SARS-CoV-2 in ddPCR (100%). Contrariwise, negative tests were observed in 95.0% ddPCR negative patients (P

Introduction: Thoracic surgery can have serious side effects. Accurate preoperative evaluation to assess which patients with anatomically resectable disease are suitable candidates for surgery is mandatory. Case description: A 58-year-old man, scheduled for left pneumonectomy for lung cancer, passed all the preoperative examinations suggested by guidelines and underwent the surgery. Three days after pneumonectomy, he experienced hemorrhagic shock and subsequent acute respiratory distress syndrome. Fifteen days after left pneumonectomy, he experienced exertional acute right heart failure (ARHF). We administered sildenafil and he improved, clinically and echocardiographically. During the following 2 years of follow-up, he was asymptomatic at rest but under exercise test, he developed pulmonary hypertension with echocardiographic signs of right ventricular impairment. Conclusions: In patients scheduled for major lung resections, preoperative stress echocardiography may give an adjunctive value to cardiopulmonary exercise test, quantifying the exercise-induced reduction in right ventricle ejection fraction and identifying asymptomatic patients at risk for postoperative ARHF.

Aim. To evaluate the correlation between insertion torque (IT) and implant stability quotient (ISQ) in tapered implants with knife-edge threads.Methods. Seventy-five identical implants (Anyridge, Megagen) were inserted by using a surgical drilling unit with torque control and an integrated resonance frequency analysis module (Implantmed, W&H). IT (N/cm) and ISQ were recorded and implants were divided into three groups (n=25) according to the IT: low (50). ISQ difference among groups was assessed by Kruskal-Wallis test, followed by Bonferroni-corrected Mann–WhitneyU-test for pairwise comparisons. The strength of the association between IT and ISQ was assessed by Spearman Rho correlation coefficient (α=0.05).Results. At the pairwise comparisons, a significant difference of ISQ values was demonstrated only between low torque and high torque groups. The strength of the association between IT and ISQ value was significant for both the entire sample and the medium torque group, while it was not significant in low and high torque groups.Conclusions. For the investigated implant, ISQ and IT showed a positive correlation up to values around 50 N/cm: higher torques subject the bone-implant system to unnecessary biological and mechanical stress without additional benefits in terms of implant stability. This trial is registered withNCT03222219.

Key Clinical Message This report describes the successful use of a new intervention to improve respiratory mechanics and gas exchange in a relatively homogeneous group of infants with severe bronchiolitis‐induced PARDS after failure of conventional treatment. These results may open a new interesting area of research and management for PARDS patients.

Purpose: This paper describes a new ultrasonic instrument (tipholder DB1 with crown prep tip inserts) designed to optimize prosthodontic margin repositioning and finishing. Materials and Methods: The insert movement was assessed, and it was demonstrated that tipholder DB1 provides its inserts with an elliptical-like movement, making the entire insert surface able to cut. Then, 20 extracted teeth were prepared using tipholder DB1, sonic instruments, and traditional drills. Dental surface roughness produced using each of the three tools was measured using a roughness tester. Results were compared using univariate analysis of variance and Bonferroni post hoc test. Results: The roughness produced using tipholder DB1 with crown prep insert presented no statistically significant differences compared to the roughness produced using sonic instruments and traditional drills. Conclusion: Tipholder DB1 with crown prep inserts is a promising treatment for margin repositioning and finishing.

Dear Editor, During critical illness, poor gut motility, increased gastric pH (due to acid suppression) and the use of broad-spectrum antibiotics destroy normal microbiota and favour overgrowth of potentially pathogenic microorganisms (PPMOs) in the gut. Bacteria reflux into the stomach and are therefore aspirated into the lungs. The major cause of ventilationassociated pneumonia (VAP) seems to be the aspiration of these microorganisms [1]. Current VAP prevention strategies (elevation of the head of the bed, special coated tracheal tubes, oral care, subglottic secretion drainage, selective digestive tract decontamination and use of sedation breaks and protocolized weaning trial) therefore aim to reduce colonisation of the oropharynx and upper gastrointestinal tract and prevent aspiration [2]. These measures have been demonstrated to lower the incidence of VAP but not enough: VAP is, and has been for years, the most common intensive care unit (ICU)-acquired infection [3]. Urgent solutions are required because VAP leads to increased length of stay, morbidity, mortality and costs [1]. Probiotics were proposed as an adjunct/alternative to maintain the normal gut microbiota, improve gut– mucosal barrier, upregulate immune response, decrease bacterial translocation and decrease biofilm production on the endotracheal tube. To date there have been 11 randomised controlled trials of probiotic therapy as a strategy to prevent VAP. The inclusion criteria, sample size, populations studied, diagnostic criteria for VAP, the probiotic used (formula, dosing and route of administration) varied between studies and may explain contrasting results. Therefore, currently, the data with probiotics are far from conclusive [4]. In a recently published article, Zeng and co-workers presented the results of another trial designed to evaluate the preventive effect of probiotics on VAP [5]. They concluded that the administration of probiotics was associated with a reduction of microbiologically confirmed VAP incidence, a delay of VAP occurrence and a reduction of gastric colonisation with PPMOs. This study has several methodological limitations, some of which were not declared by the authors. Oxygenation deterioration is not considered in VAP diagnostic criteria, and a persistent infiltrate may lead to a diagnosis of new-onset pneumonia. The slow enrolment rate (4.5 pts/ICU/year) may be a bias of the study. The decision to end the study 14 days after enrolment and not at ICU discharge is difficult to understand. Probiotics reduced VAP incidence but were ineffective on antibiotics use, and so what do we gain? The authors should clarify whether, at least, the use of antibiotics to treat lung infections decreased. Furthermore, we must bear in mind that this trial was conducted in ICUs with VAP prevalence of 60 %. In a similar scenario, it is easier to establish a beneficial effect of treatment. Conclusions, therefore, cannot be generalized to ICUs where VAP incidence is lower. Despite these limitations, we are grateful to the authors for trying to break new ground in the VAP probiotics jungle. Unfortunately, to date and even after this study, it is still not known whether probiotics are definitely effective in preventing VAP. However, they can be considered safe and inexpensive. In an era of increasing antibiotic resistance and limited new antibiotics, infection prevention is mandatory and probiotics may play a significant role. *Correspondence: jacopo.colombo@unimi.it 1 Department of Pathophysiology and Transplantation, University of Milan, Via Festa del Perdono 3, Milan, Italy Full author information is available at the end of the article

Fungi are an increasingly frequent etiology of infections in immunocompromised host and in critically ill patients causing substantial morbidity and mortality. Recent epidemiological studies have shown that approximately 15% of healthcare-associated infections are caused by fungi.

Ex vivo lung perfusion (EVLP) has been validated as a valuable technique to increase the pool of organs available for lung transplantation.After a preclinical experience, we obtained permission from the Ethics Committee of our institution to transplant lungs after EVLP reconditioning. ABO compatibility, size match, and donor arterial oxygen pressure (PaO(2))/fraction of inspired oxygen (FiO(2)) ≤ 300 mm Hg were considered to be inclusion criteria, whereas the presence of chest trauma and lung contusion, evidence of gastric content aspiration, pneumonia, sepsis, or systemic disease were exclusion criteria. We only considered subjects on an extra corporeal membrane oxygenation (ECMO) bridge to transplantation with rapid functional deterioration. Using Steen solution with packed red blood cells oxygenated with 21% O(2), 5% to 7% CO(2) was delivered, targeted with a blood flow of approximately 40% predicted cardiac output. Once normothermic, the lungs were ventilated with a tidal volume of 7 mL/kg a PEEP of 5 cmH(2)O and a respiratory rate of 7 bpm. Lungs were considered to be suitable for transplantation if well oxygenated [P(v-a) O(2)350 mm Hg on FiO(2) 100%], in the absence of deterioration of pulmonary vascular resistance and lung mechanics over the perfusion time.From March to September 2011, six lung transplantations were performed, including two with EVLP. The functional outcomes were similar between groups: at T72 posttransplantation, the median PaO(2)/FiO(2) were 306 mm Hg (range, 282 to 331 mm Hg) and 323 mm Hg (range, 270 to 396 mm Hg) (P = 1, EVLP versus conventional). Intensive care unit ICU and hospital length of stay were similar (P = .533 and P = .663, respectively) with no mortality at 60 days in both groups. EVLP donors were older (49 ± 6 y versus 21 ± 7 y, P.05), less well oxygenated (184 ± 6 mm Hg versus 570 ± 30, P.05), displaying higher Oto scores (9.5 ± 0.7 versus 1.7 ± 1.5, P.05).The first 6 months of the EVLP program allowed us to increase the number of organs available for transplantation with short-term outcomes comparable to conventional transplantations.