Neurological complications in pediatric patients with SARS-CoV-2 infection: a systematic review of the literature.

OBJECTIVES: To describe clinical characteristics, laboratory tests, radiological data and outcome of pediatric cases with SARS-CoV-2 infection complicated by neurological involvement. STUDY DESIGN: A computerized search was conducted using PubMed. An article was considered eligible if it reported data on pediatric patient(s) with neurological involvement related to SARS-CoV-2 infection. We also described a case of an acute disseminated encephalomyelitis (ADEM) in a 5-year-old girl with SARS-CoV-2 infection: this case was also included in the systematic review. RESULTS: Forty-four articles reporting 59 cases of neurological manifestations in pediatric patients were included in our review. Most (32/59) cases occurred in the course of a multisystem inflammatory syndrome in children (MIS-C). Neurological disorders secondary to cerebrovascular involvement were reported in 10 cases: 4 children with an ischemic stroke, 3 with intracerebral hemorrhage, 1 with a cerebral sinus venous thrombosis, 1 with a subarachnoid hemorrhage, 1 with multiple diffuse microhemorrhages. Reversible splenial lesions were recognized in 9 cases, benign intracranial hypertension in 4 patients, meningoencephalitis in 4 cases, autoimmune encephalitis in 1 girl, cranial nerves impairment in 2 patients and transverse myelitis in 1 case. Five cases had Guillain-Barré syndrome (GBS) and two, including ours, had ADEM. Radiological investigations were performed in almost all cases (45/60): the most recurrent radiological finding was a signal change in the splenium of the corpus callosum. The presence of SARS-CoV-2 viral nucleic acid in the cerebrospinal fluid was proved only in 2 cases. The outcome was favorable in almost all, except in 5 cases. CONCLUSIONS: Our research highlights the large range of neurological manifestations and their presumed pathogenic pathways associated with SARS-CoV-2 infection in children. Nervous system involvement could be isolated, developing during COVID-19 or after its recovery, or arise in the context of a MIS-C. The most reported neurological manifestations are cerebrovascular accidents, reversible splenial lesions, GBS, benign intracranial hypertension, meningoencephalitis; ADEM is also a possible complication, as we observed in our patient. Further studies are required to investigate all the neurological complications of SARS-CoV-2 infection and their underlying pathogenic mechanism.

Ligasure impact™ might reduce blood loss, complications, and re-operation occurrence after abdominoplasty in massive-weight-loss patients: A Comparative Study.

BACKGROUND AND AIMS: The most effective dissection technique for raising the flap in abdominoplasty is still controversial, particularly in high-risk massive-weight-loss patients. LigaSure Impact™ vessel-sealing system (Medtronic, Dublin, Ireland) is an energy device commonly used among different surgical specialties to reduce morbidity and implement outcomes. The aim of this study was to investigate the effectiveness of LigaSure Impact in abdominoplasty compared with the conventional techniques, diathermia. MATERIAL AND METHODS: Patients underwent primary abdominoplasty after massive weight loss at a single center from 1 January 2008 to 31 May 2015 and were retrospectively reviewed. A total of 94 patients eligible for the study were divided into two groups on basis of the dissection technique: LigaSure Impact group (29 patients) and the conventional technique group (65 patients). Total intraoperative blood loss was the primary endpoint. Duration of the operation, perioperative complications and re-operation were recorded as secondary endpoints. RESULTS: Baseline characteristics were well balanced between the groups. Significant differences were found in intraoperative blood loss favoring LigaSure Impact group (259.6 ± 198.8 mL vs 377.9 ± 190.0 mL, p = 0.004) and blood transfusion rates (13.8% vs 35.4%, p = 0.047). In contrast, operative time was significantly longer in LigaSure Impact group (168.6 ± 121.2 vs 179.7 ± 57.6 min, p = 0.005), while a tendency to shorter hospital stay was found in LigaSure Impact group (3.6 ± 1.1 days vs 4.6 ± 3.2 days, p = 0.081). Overall complications occurrence, Clavien-Dindo grade II (24.1% vs 55.4%) and grade III (13.8% vs 30.8%) complications were significantly lower in LigaSure Impact group (respectively, p = 0.005, p = 0.007, p = 0.016). Late (>30 days) re-operation rate was significantly lower in the LigaSure Impact group (6.9% vs 27.70%, p = 0.0028). Specific wound complications showed no significant difference. CONCLUSION: LigaSure Impact vessel-sealing system may be beneficial in improving abdominoplasty outcomes in massive-weight-loss patients because it might reduce blood loss, need for transfusions, complications, and re-operations.

Testing a novel biotechnological passive sampler for monitoring atmospheric PAH pollution.

In this study we evaluated a new type of passive air sampler, the "mossphere" device, filled with a Sphagnum palustre clone. For this purpose, we compared the atmospheric levels of polyaromatic hydrocarbons (PAHs) collected using this device and those collected in conventional bulk deposition and particulate matter (PM10) samplers. All three types of samplers were exposed at 10 sites affected by different levels of pollution and located in two different climate zones. The bulk deposition/ mossphere comparison yielded a greater number of significant regressions with higher coefficients of determination than the PM10/ mossphere comparison. No significant regressions were observed for 3-ring PAHs in either comparison. The mosspheres explain ca. 50% of the variability of the concentrations of 4-, 5- and 6-ring PAHs and total PAHs detected in PM10 and ca. 70% of the corresponding concentrations detected in the bulk deposition. The use of the Sphagnum clone enables standardization of the set-up, thus making the mossphere device a good sampling tool for monitoring 4-, 5- and 6-ring and total PAHs, especially those associated with bulk deposition. The findings indicate the potential usefulness of this innovative technology for mapping PAH levels.

Systematic reappraisal of the reverse-flow medial plantar flap: From vascular anatomical concepts to surgical applications.

INTRODUCTION: The medial plantar artery (MPA) flap in its anterograde form is considered the gold standard for heel reconstruction. This flap can be also raised distally for the reconstruction of the weight-bearing forefoot. However, terminal branches of the MPA, together with their connection with distal and dorsal systems, can be variable. Our objective was to provide a comprehensive anatomic description that could match all technical possibilities in raising the distally based MPA flap. A systematic review of indication outcomes and complications of the distally based MPA flap is provided. METHODS: According to PRISMA criteria, we systematically reviewed previous literature using the MEDLINE database concerning the MPA flap from 1977 to November 2018 using the keywords « Medial plantar flap ¼ OR « Medial Plantar Artery ¼. Anatomic variations, techniques, indications, outcomes, and complications were analyzed. RESULTS: All different vascular pedicles that may be used for the vascularization of the MPA flap were classified. Apart from the flap with a proximal flow, there may be five anastomotic connections from the superficial MPA to the plantar arterial network. Four dorso-plantar links supply the plantar network thanks to dorsal vascularization. Literature analysis of outcomes showed how the retrograde MPA flap may be unreliable with 14% of venous congestion rate and 9.3% of average flap loss, for a total average flap complication of 18.6%. CONCLUSION: This review provides the ultimate, clear picture of the complex anastomosis of the forefoot, with direct referral to surgical flap raising techniques, guiding surgeons during challenging reconstructions.

Indoor vs. outdoor airborne element array: A novel approach using moss bags to explore possible pollution sources.

This study investigated by the moss-bag approach the pattern of air dispersed elements in 12 coupled indoor/outdoor exposure sites, all located in urban and rural residential areas. The aims were to discriminate indoor vs. outdoor element composition in coupled exposure sites and find possible relation between moss elemental profile and specific characteristics of each exposure site. Elements were considered enriched when in 60% of the sites, post-exposure concentration exceeded pre-exposure concentration plus two folds the standard deviation. Of the 53 analyzed elements, 15 (As, B, Ca, Co, Cr, Cu, Mn, Mo, Ni, Sb, Se, Sn, Sr, V, Zn) were enriched in moss exposed outdoor, whereas a subset of 7 elements (As, B, Cr, Mo, Ni, Se, V) were enriched also in indoor moss samples. The cluster analysis of the sites based on all elements, clearly separated samples in two groups corresponding to mosses exposed indoor and outdoor, with the latter generally exceeding the first. Among outdoor sites, urban were most impacted than rural; whereas other factors (e.g., heating and cooking systems, building material, residence time and family life style) could affect element profile of indoor environments. Based on the indoor/outdoor ratio, As derived from outdoor and indoor sources, B, Mo and Se were enriched mostly in outdoor sites; Ni, Cr and V were specifically enriched in most indoor samples, supporting the presence of indoor emitting sources for these elements. A PCA of all indoor sites based on enriched elements and site characteristics showed that traffic affected indoor pollution in urban areas. The moss bag approach provided useful information for a global assessment of human exposure.

Platelet-rich plasma versus hyaluronic acid injections for knee osteoarthritis: a propensity-score analysis.

BACKGROUND AND AIMS: Intra-articular injections of viscosupplements have been an option in the treatment of knee osteoarthritis. Platelet-rich plasma is an experimental treatment in osteoarthritis. Previous studies have shown that platelet-rich plasma reduces osteoarthritis symptoms in similar proportions as viscosupplements. The aim of this study was to compare platelet-rich plasma versus viscosupplements in terms of symptoms' relief and time to arthroplasty. MATERIAL AND METHODS: A total of 190 patients included in this retrospective study received either intra-articular injections of platelet-rich plasma (94 patients) or hyaluronic acid (86 patients) between January 2014 and October 2017. Western Ontario and McMaster Universities Osteoarthritis Index, Visual Analogue Scale, and range of motion were measured before injection, at 15 days, 6 months, 12 months, and at last follow-up. We compared outcomes between these two groups using propensity score analysis for risk adjustment in multivariate analysis and for one-to-one matching. RESULTS: Hyaluronic acid-treated patients experienced a higher arthroplasty rate (36.0% vs 5.3%, p < 0.001), lower range of motion, worse Visual Analogue Scale and Western Ontario and McMaster Universities Osteoarthritis Index scores, and increased risk of any arthroplasty occurrence (log-rank < 0.001) than platelet-rich plasma patients. Cox proportional hazards analysis revealed a tendency to decrease the risk of knee arthroplasty for the patients treated by platelet-rich plasma (hazard ratio = 0.23, 95% confidence interval, 0.05-1.05, p = 0.058). When the treatment method was adjusted for propensity score in the propensity score-matched pairs (n = 78), we found that platelet-rich plasma group still showed significant improvement over the hyaluronic acid group in arthroplasty rate (12.8% vs 41.0%, p = 0.010), Visual Analogue Scale and Western Ontario and McMaster Universities Osteoarthritis Index scores, but not in the range of motion, during the mean follow-up of 16.7 months. CONCLUSION: Intra-articular injections of platelet-rich plasma associated with better outcomes than hyaluronic acid in knee osteoarthritis. Platelet-rich plasma might prolong the time to arthroplasty and provide a valid therapeutic option in selected patients with knee osteoarthritis not responding to conventional treatments. Further larger studies are needed to validate this promising treatment modality.

Hypovitaminosis D: comparison between patients with hip fracture and patients with vertebral fractures.

This study analyses the difference in 25OH-vitamin D values between two groups of patients both affected by severe osteoporosis with fragility fractures, but one group has vertebral fractures and the other one has hip fractures. Patients with hip fractures have vitamin D values lower than patients with vertebral fractures. INTRODUCTION: The purpose of this study was to evaluate 25OHD levels in patients with fragility vertebral fractures (VF) and hip fractures (HF) and make a comparison between the groups. METHODS: In the first group were enrolled ambulatory patients with 3 or more moderate to severe VF; in the second group were enrolled patients hospitalized in the Department of Orthogeriatrics undergoing surgery for HF. For all patients, we collected values of 25OHD and PTH. The group of patients with VF was further subdivided into pre-existing VF or recent VF treated within 30 days with vertebroplasty. RESULTS: The sample consists of 180 subjects divided into two groups: 90 with VF and 90 with HF. The average value of 25OHD in the total sample was 13.2 ± 9.6 ng/ml, Vitamin D was significantly lower in the HF group than the VF group (p < 0.001)(VF 18.6 ± 9.7 ng/ml, HF 7.9 ± 5.7 ng/ml). The mean PTH value in the total sample was 67.5 ± 54.9 pg/ml and PTH was significantly higher in the HF group compared to the group with VF (p < 0.001) (VF 55.6 ± 27.2 pg/ml, HF 78.7 ± 70.2 pg/ml). The mean 25OHD value in the recent VF group is 16.0 ± 6.6 ng/ml while in the pre-existing VF group is 19.5 ± 10.4 ng/ml with a statistically significant difference (p < 0.001). CONCLUSIONS: Patients of the same age with severe osteoporosis have a lower 25OHD value when the fracture occur at the hip and is recent, probably this is due to the inflammation caused by fracture and/or surgical intervention.

Evidence on the effectiveness of mosses for biomonitoring of microplastics in fresh water environment.

Mosses are well known as biomonitors of fresh water for metal pollutants, but no studies were reported so far about their ability to intercept plastic particles, although this kind of pollution has become an urgent issue worldwide. In the present work, the interaction between the moss Sphagnum palustre L. cultured in vitro and polystyrene nanoparticles (NPs) was studied for the first time in a laboratory experiment, in the view of using moss transplants for detecting microplastics in fresh water environments. The ability of S. palustre to intercept and retain polystyrene, and the effects of vitality and post-exposure washing on NP retention by moss were tested. Fluorescence microscope observations showed that polystyrene NPs were retained by moss leaves in form of small (the most abundant fraction) and large aggregates. Particle count analysis highlighted that the number of particles increased while increasing the exposure time. Moreover, moss devitalization favored NP accumulation, likely because of cell membrane damages occurred in dead moss material. Post-exposure washing induced a loss of larger aggregates, suggesting that exposure time is a key point to be carefully evaluated in field conditions. These results encourage the use of S. palustre transplants for monitoring microplastics contamination of fresh water environments.

Geochemistry and carbon isotopic ratio for assessment of PM10 composition, source and seasonal trends in urban environment.

Investigating the nature of PM10 is crucial to differentiate sources and their relative contributions. In this study we compared the levels, and the chemical and mineralogical properties of PM10 particles sampled in different seasons at monitoring stations representative of urban background, urban traffic and suburban traffic areas of Naples city. The aims were to relate the PM10 load and characteristics to the location of the monitoring stations, to investigate the different sources contributing to PM10 and to highlight PM10 seasonal variability. Bulk analyses of chemical species in the PM10 fraction included total carbon and nitrogen, δ13C and other 20 elements. Both natural and anthropogenic sources were found to contribute to the exceedances of the EU PM10 limit values. The natural contribution was mainly related to marine aerosols and soil dust, as highlighted by X-ray diffractometry and SEM-EDS microscopy. The percentage of total carbon suggested a higher contribution of biogenic components to PM10 in spring. However, this result was not supported by the δ13C values which were seasonally homogeneous and not sufficient to extract single emission sources. No significant differences, in terms of PM10 load and chemistry, were observed between monitoring stations with different locations, suggesting a homogeneous distribution of PM10 on the studied area in all seasons. The anthropogenic contribution to PM10 seemed to dominate in all sites and seasons with vehicular traffic acting as a main source mostly by generation of non-exhaust emissions Our findings reinforce the need to focus more on the analysis of PM10 in terms of quality than of load, to reconsider the criteria for the classification and the spatial distribution of the monitoring stations within urban and suburban areas, with a special attention to the background location, and to emphasize all the policies promoting sustainable mobility and reduction of both exhaust and not-exhaust traffic-related emissions.

Performance of three cardoon cultivars in an industrial heavy metal-contaminated soil: Effects on morphology, cytology and photosynthesis.

In the present work the cytomorphological and physiological effects on three cardoon cultivars - Sardo, Siciliano, Spagnolo - grown in a metal-polluted soil, were investigated, to assess the traits concurring to the high tolerance to metal stress observed in cv. Spagnolo compared to the other two cultivars. The plants were grown for one month on a real polluted soil collected at a dismantling battery plant, highly enriched by heavy metals, especially Cd and Pb, and their leaves were analyzed by a multidisciplinary approach. TEM observations highlighted severe ultrastructural damage in Sardo and Siciliano, and preserved cytological traits in Spagnolo. Both pigment content and photochemistry indicated a decline in photosynthesis in Sardo and Sicilano and a substantial stability of the same parameters in Spagnolo. Protein analysis indicated a decrease in D1 level in all cultivars; in Spagnolo the D1 decrease was more pronounced and associated to a significant increase in Rubisco, a pattern likely preserving photosynthetic efficiency and high biomass production. In conclusion, Spagnolo cardoon was able to face metal stress through a prompt, multiple response balancing structural and functional traits.

Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program.

Background: Male breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period. Methods: Patients with follow-up and tumor samples, treated between 1990 and 2010, in 93 centers/9 countries. Samples were centrally analyzed in three laboratories (the United Kingdom, the Netherlands and the United States). Results: Of 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001 and 2010, 57 (5.1%) had metastatic disease (M1). Median age at diagnosis: 68.4 years. Of 1054 M0 cases, 56.2% were node-negative (N0) and 48.5% had T1 tumors; 4% had breast conserving surgery (BCS), 18% sentinel lymph-node biopsy; half received adjuvant radiotherapy; 29.8% (neo)adjuvant chemotherapy and 76.8% adjuvant endocrine therapy (ET), mostly tamoxifen (88.4%). Per central pathology, for M0 tumors: 84.8% ductal invasive carcinomas, 51.5% grade 2; 99.3% estrogen receptor (ER)-positive; 81.9% progesterone receptor (PR)-positive; 96.9% androgen receptor (AR)-positive [ER, PR or AR Allred score ≥3]; 61.1% Ki67 expression low (<14% positive cells); using immunohistochemistry (IHC) surrogates, 41.9% were Luminal-A-like, 48.6% Luminal-B-like/HER-2-negative, 8.7% HER-2-positive, 0.3% triple negative. Median follow-up: 8.2 years (0.0-23.8) for all, 7.2 years (0.0-23.2), for M0, 2.6 years (0.0-12.7) for M1 patients. A significant improvement over time was observed in age-corrected BC mortality. BC-specific-mortality was higher for men younger than 50 years. Better overall (OS) and recurrence-free survival (RFS) were observed for highly ER+ (P = 0.001), highly PR+ (P = 0.002), highly AR+ disease (P = 0.019). There was no association between OS/RFS and HER-2 status, Ki67, IHC subtypes nor grade. Conclusions: Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in >90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.

Laparoscopic Roux-En-Y Gastric Bypass in Elderly Patients (60 Years or Older): A Meta-Analysis of Comparative Studies.

BACKGROUND AND AIMS: Elderly patient might experience an increased risk of complications after laparoscopic Roux-en-Y gastric bypass. We aimed to perform a meta-analysis of comparative studies on this issue in patients aged 60 years or older. MATERIAL AND METHODS: A systematic literature search was performed. Medline, Cochrane Library, Embase, Scopus, and Google Scholar were searched until July 2016 for studies on outcomes of laparoscopic Roux-en-Y gastric bypass in elderly versus younger patients. Primary outcomes were mortality and overall complications. Secondary outcomes were length of hospital stay, excess weight loss percentage, effect on diabetes, hypertension, hyperlipidemia and obstructive sleep apnea. Heterogeneity across the studies was evaluated by the I2 test, and a random effects model was used. Results were expressed as mean difference and risk ratio (RR). RESULTS: Seven studies involving 3128 patients were retrieved and included in this study. A significantly increased risk of mortality and overall complications was observed among patients older than 60 years compared with younger ones (RR, 6.12; 95% confidence interval 1.08-34.83; p = 0.04; RR, 1.51; 95% confidence interval 1.07-2.11; p = 0.02). Particularly, elderly patients experienced 1% increased risk of mortality and 3% increased risk of overall complications. Length of stay, diabetes, and obstructive sleep apnea remission rates were similar among the groups. Excess weight loss percentage was significantly greater among younger patients (mean difference, -3.44; 95% confidence interval -5.20, -1.68; p < 0.001), as were hypertension (RR, 0.57; 95% confidence interval 0.42-0.76; p < 0.001) and hyperlipidemia (RR, 0.61; 95% confidence interval 0.45-0.83; p = 0.002) remission rates. CONCLUSION: Laparoscopic Roux-en-Y gastric bypass in patients older than 60 years may be a risky bariatric surgery operation due to higher complications and mortality and may not be as effective as in patients younger than 60 years. Thus, older patients should be carefully counseled before this procedure for individual risk-benefit assessment.

Ultrastructural, protein and photosynthetic alterations induced by Pb and Cd in Cynara cardunculus L., and its potential for phytoremediation.

The effects of cadmium and lead were investigated in Cynara cardunculus L. Plant uptake by root and shoot, changes in cell ultrastructure and photosynthetic efficiency, photosynthetic key protein levels, as well as regulation of stress-induced Hsp70 were examined. Cynara cardunculus accumulated Cd and Pb in their tissue, with a different trend for the two metals. The prompt translocation of Cd to the shoot may justify the ultrastructural injuries, especially observed in chloroplasts. However, Cd- treated plants did not show any decline in photochemistry; it is likely that Cd in shoot tissue triggers defense mechanisms, increasing the level of proteins involved in photosynthesis (i.e., Rubisco and D1 increased 7 and 4.5 fold respectively) as a compensatory response to neutralize chloroplast damage. The accumulation of Pb mainly in root, can explain the increase in Hsp70 level (23 folds) in this tissue. Pb reached the shoots, even at low amounts, causing an overall significant change in some photochemical parameters (QY and NPQ decreases and increases of 25%, respectively). The results suggest a higher sensitivity of C. cardunculus to Pb than Cd, although maximal photochemical efficiency suggests that this species seems to tolerate Pb and Cd and hence, it is a suitable candidate for phytoremediation.

Sphagnum palustre clone vs native Pseudoscleropodium purum: A first trial in the field to validate the future of the moss bag technique.

Although a large body of literature exists on the use of transplanted mosses for biomonitoring of air pollution, no article has addressed so far the use and the accumulation performance of a cloned moss for this purpose. In this work, a direct comparison of metal accumulation between bags filled with a Sphagnum palustre L. clone or with native Pseudoscleropodium purum Hedw., one of the most used moss species in biomonitoring surveys, was investigated. The test was performed in sites with different atmospheric contamination levels selected in urban, industrial, agricultural and background areas of Italy and Spain. Among the eighteen elements investigated, S. palustre was significantly enriched in 10 elements (Al, Ba, Cr, Cu, Fe, Hg, Pb, Sr, V and Zn), while P. purum was enriched only in 6 elements (Al, Ba, Cu, Hg, Pb and Sr), and had a consistently lower uptake capacity than S. palustre. The clone proved to be more sensitive in terms of metal uptake and showed a better performance as a bioaccumulator, providing a higher accumulation signal and allowing a finer distinction among the different land uses and levels of pollution. The excellent uptake performance of the S. palustre clone compared to the native P. purum and its low and stable baseline elemental content, evidenced in this work, are key features for the improvement of the moss bag approach and its large scale application.

Dual MET/EGFR therapy leads to complete response and resistance prevention in a MET-amplified gastroesophageal xenopatient cohort.

Amplification of the MET oncogene occurs in 2-4% of gastroesophageal cancers and defines a small and aggressive subset of tumors. Although in vitro studies have given very promising results, clinical trials with MET inhibitors have been disappointing, showing few and short lasting responses. The aim of the work was to exploit a MET-amplified patient-derived xenograft model to optimize anti-MET therapeutic strategies in gastroesophageal cancer. We found that despite the high MET amplification level (26 gene copies), in the absence of qualitative or quantitative alterations of EGFR, MET inhibitors induced only tumor growth inhibition, whereas dual MET/EGFR inhibition led to complete tumor regression. Importantly, the combo treatment completely prevented the onset of resistance, which quite rapidly appeared in tumors treated with MET monotherapy. We found that this secondary resistance was due to EGFR activation and could be overcome by dual MET/EGFR inhibition. Similar results were also obtained in a MET-addicted, established gastric cancer cell line. In vitro experiments performed on tumor-derived primary cells confirmed that MET inhibitors were not able to abrogate the activation of downstream transducers and that only the combined MET/EGFR treatment completely shut off the signaling. Previously reported cases, as well as those described here, showed only partial and transient sensitivity to anti-MET therapy. The finding that combined anti-MET/EGFR therapy-even in the absence of EGFR genetic alterations-induced complete and durable response, represents a proof of concept and guarantees further investigations, opening a new perspective of treatment for these patients.

Tracking the route of phenanthrene uptake in mosses: An experimental trial.

In recent decades, mosses have been used as native species or as transplants in monitoring a wide range of pollutants from inorganic (i.e. metals and metalloids) to organic contaminants (mainly polycyclic aromatic hydrocarbons-PAHs). To implement the use of mosses as biomonitors of PAHs, one important issue is the study of the interactions between these compounds and moss tissues. In this study we investigated the mode of phenanthrene uptake in four moss species (Amblystegium humile, Plagiomnium affine, Hypnum cupressiforme and a clone of Sphagnum palustre) and its movements from air to plant surface and within the biomonitors, using fluorescent and confocal microscopy. The target compound, partitioned between gas and particulate phase depending on air conditions, was selected since it is one of the most abundant PAHs released into the atmosphere. Our findings support the hypothesis that phenanthrene aggregates in particles and in this form it is chiefly intercepted and uptaken onto moss surfaces, albeit with different frequency in the four species, with S. palustre>H. cupressiforme>P. affine=A. humile. Phenanthrene enters the dead, empty hyalocysts of S. palustre. Specific surface area and composition, frequency and distribution of binding groups may also explain the different ability of phenanthrene uptake by the four moss species.

3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors.

Mass Spectrometry Imaging (MSI) is a widespread technique used to qualitatively describe in two dimensions the distribution of endogenous or exogenous compounds within tissue sections. Absolute quantification of drugs using MSI is a recent challenge that just in the last years has started to be addressed. Starting from a two dimensional MSI protocol, we developed a three-dimensional pipeline to study drug penetration in tumors and to develop a new drug quantification method by MALDI MSI. Paclitaxel distribution and concentration in different tumors were measured in a 3D model of Malignant Pleural Mesothelioma (MPM), which is known to be a very heterogeneous neoplasm, highly resistant to different drugs. The 3D computational reconstruction allows an accurate description of tumor PTX penetration, adding information about the heterogeneity of tumor drug distribution due to the complex microenvironment. The use of an internal standard, homogenously sprayed on tissue slices, ensures quantitative results that are similar to those obtained using HPLC. The 3D model gives important information about the drug concentration in different tumor sub-volumes and shows that the great part of each tumor is not reached by the drug, suggesting the concept of pseudo-resistance as a further explanation for ineffective therapies and tumors relapse.