Author Correction: Forearc carbon sink reduces long-term volatile recycling into the mantle.

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

Hypnotic communication for periprocedural analgesia during transcatheter ablation of atrial fibrillation.

INTRODUCTION: Hypnosis is a therapeutic strategy for pain control. We aimed at investigating the use of this technique in a large population undergoing atrial fibrillation (AF) ablation. METHODS: 70 consecutive AF patients referred for transcatheter ablation, underwent hypnotic communication for periprocedural analgesia (Group A), were compared with 70 patients undergoing conventional analgesia (Group B). Procedural data, anxiety, perceived pain, perceived procedural duration and the dosages of administered analgesic drugs were compared using validated score scales. RESULTS: Hypnotic communication (Group A) resulted in a significant procedural-related anxiety reduction (Pre procedural 4.7 ±â€¯2.9 Vs Intra Procedural 0.8 ±â€¯1.2, P < 0.001) and perceived procedural duration (Real length 108 ±â€¯33 min Vs Perceived Length 77 ±â€¯39 min, P < 0.001). Group A patients reported a painless procedure in 78% (Pain scale ≤2). Regarding analgesic drug, Group A used only Fentanyl and Paracetamol. The Fentanyl dosage was similar in Group A and B (mean 0.142 Vs 0.146 mg, P = 0.65) while higher Paracetamol dosage was reported in Group A (mean 853 Vs 337 mg, P < 0.001). Group B also used Midazolam (mean 1.8 mg), Propofol (mean 43.8 mg) and narcosis was required in 2 patients. Total radiofrequency (RF) delivered time did not differ between the two groups (mean 28.9 Vs 27.6 min, P = 0.623) as well as mean RF power (mean 35.3 Vs 35.5 W, P = 0.424). No complications occurred. CONCLUSION: Hypnotic communication during AF ablation was related to a significant reduction of intra-procedural anxiety, perceived pain, procedural analgesic drugs dosage and perceived procedural duration without affecting total RF delivered time and procedural safety.

Author Correction: Forearc carbon sink reduces long-term volatile recycling into the mantle.

Change history: In this Article, the original affiliation 2 was not applicable and has been removed. In addition, in the Acknowledgements there was a statement missing and an error in a name. These errors have been corrected online.

Antibacterial coating of implants: are we missing something?

Implant-related infection is one of the leading reasons for failure in orthopaedics and trauma, and results in high social and economic costs. Various antibacterial coating technologies have proven to be safe and effective both in preclinical and clinical studies, with post-surgical implant-related infections reduced by 90% in some cases, depending on the type of coating and experimental setup used. Economic assessment may enable the cost-to-benefit profile of any given antibacterial coating to be defined, based on the expected infection rate with and without the coating, the cost of the infection management, and the cost of the coating. After reviewing the latest evidence on the available antibacterial coatings, we quantified the impact caused by delaying their large-scale application. Considering only joint arthroplasties, our calculations indicated that for an antibacterial coating, with a final user's cost price of €600 and able to reduce post-surgical infection by 80%, each year of delay to its large-scale application would cause an estimated 35 200 new cases of post-surgical infection in Europe, equating to additional hospital costs of approximately €440 million per year. An adequate reimbursement policy for antibacterial coatings may benefit patients, healthcare systems, and related research, as could faster and more affordable regulatory pathways for the technologies still in the pipeline. This could significantly reduce the social and economic burden of implant-related infections in orthopaedics and trauma. Cite this article: C. L. Romanò, H. Tsuchiya, I. Morelli, A. G. Battaglia, L. Drago. Antibacterial coating of implants: are we missing something? Bone Joint Res 2019;8:199-206. DOI: 10.1302/2046-3758.85.BJR-2018-0316.

Forearc carbon sink reduces long-term volatile recycling into the mantle.

Carbon and other volatiles in the form of gases, fluids or mineral phases are transported from Earth's surface into the mantle at convergent margins, where the oceanic crust subducts beneath the continental crust. The efficiency of this transfer has profound implications for the nature and scale of geochemical heterogeneities in Earth's deep mantle and shallow crustal reservoirs, as well as Earth's oxidation state. However, the proportions of volatiles released from the forearc and backarc are not well constrained compared to fluxes from the volcanic arc front. Here we use helium and carbon isotope data from deeply sourced springs along two cross-arc transects to show that about 91 per cent of carbon released from the slab and mantle beneath the Costa Rican forearc is sequestered within the crust by calcite deposition. Around an additional three per cent is incorporated into the biomass through microbial chemolithoautotrophy, whereby microbes assimilate inorganic carbon into biomass. We estimate that between 1.2 × 108 and 1.3 × 1010 moles of carbon dioxide per year are released from the slab beneath the forearc, and thus up to about 19 per cent less carbon is being transferred into Earth's deep mantle than previously estimated.

The changing scenario of 1st line therapy in non-oncogene addicted NSCLCs in the era of immunotherapy.

During the last two decades front-line treatment of metastatic Non Small Cell Lung Cancer (NSCLC) has profoundly changed moving from the old "one size fits all" concept to a "histology-based" approach and then, for a small subgroup of patients to a "molecularly-selected" one. The development of immune checkpoint inhibitors and the unprecedented results reported in 2nd/3rd line prompted the evaluation of these novel therapeutic agents in chemotherapy-naïve patients either alone or in combination with platinum-based chemotherapy. Several randomized trials are evaluating the impact of immune-checkpoint inhibitors in 1st line and some of them have yet produced preliminary evidence of efficacy. However, still a long way to go and several questions are still unanswered, including proper patients selection, optimal sequential/combinatorial use of these agents, appropriate treatment duration, and finally the identification of predictive biomarkers. The aim of this paper is to provide a comprehensive overview on the growing role of immune checkpoint inhibitors in the upfront treatment of advanced non-oncogene addicted NSCLC either as single agent or in combination with other agents.

The survival impact of neoadjuvant hormonal therapy before radical prostatectomy for treatment of high-risk prostate cancer.

BACKGROUND: Several randomized controlled trials assessed the outcomes of patients treated with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP). The majority of them included mainly low and intermediate risk prostate cancer (PCa) without specifically assessing PCa-related death (PCRD). Thus, there is a lack of knowledge regarding a possible effect of NHT on PCRD in the high-risk PCa population. We aimed to analyze the effect of NHT on PCRD in a multicenter high-risk PCa population treated with RP, using a propensity-score adjustment. METHODS: This is a retrospective multi-institutional study including patients with high-risk PCa defined as: clinical stage T3-4, PSA >20 ng ml-1 or biopsy Gleason score 8-10. We compared PCRD between RP and NHT+RP using competing risks analysis. Correction for group differences was performed by propensity-score adjustment. RESULTS: After application of the inclusion/exclusion criteria, 1573 patients remained for analysis; 1170 patients received RP and 403 NHT+RP. Median follow-up was 56 months (interquartile range 29-88). Eighty-six patients died of PCa and 106 of other causes. NHT decreased the risk of PCRD (hazard ratio (HR) 0.5; 95% confidence interval (CI) 0.32-0.80; P=0.0014). An interaction effect between NHT and radiotherapy (RT) was observed (HR 0.3; 95% CI 0.21-0.43; P<0.0008). More specifically, of patients who received adjuvant RT, those who underwent NHT+RP had decreased PCRD rates (2.3% at 5 year) compared to RP (7.5% at 5 year). The retrospective design and lack of specific information about NHT are possible limitations. CONCLUSIONS: In this propensity-score adjusted analysis from a large high-risk PCa population, NHT before surgery significantly decreased PCRD. This effect appeared to be mainly driven by the early addition of RT post-surgery. The specific sequence of NHT+RP and adjuvant RT merits further study in the high-risk PCa population.

Recurrent pericarditis.

Recurrent pericarditis is the most troublesome complication of pericarditis occurring in 15 to 30% of cases. The pathogenesis is often presumed to be immune-mediated although a specific rheumatologic diagnosis is commonly difficult to find. The clinical diagnosis is based on recurrent pericarditis chest pain and additional objective evidence of disease activity (e.g. pericardial rub, ECG changes, pericardial effusion, elevation of markers of inflammation, and/or imaging evidence of pericardial inflammation by CT or cardiac MR). The mainstay of medical therapy for recurrent pericarditis is aspirin or a non-steroidal anti-inflammatory drug (NSAID) plus colchicine. Second-line therapy is considered after failure of such treatments and it is generally based on low to moderate doses of corticosteroids (e.g. prednisone 0.2 to 0.5 mg/kg/day or equivalent) plus colchicine. More difficult cases are treated with combination of aspirin or NSAID, colchicine and corticosteroids. Refractory cases are managed by alternative medical options, including azathioprine, or intravenous human immunoglobulins or biological agents (e.g. anakinra). When all medical therapies fail, the last option may be surgical by pericardiectomy to be recommended in well-experienced centres. Despite a significant impairment of the quality of life, the most common forms of recurrent pericarditis (usually named as "idiopathic recurrent pericarditis" since without a well-defined etiological diagnosis) have good long-term outcomes with a negligible risk of developing constriction and rarely cardiac tamponade during follow-up. The present article reviews current knowledge on the definition, diagnosis, aetiology, therapy and prognosis of recurrent pericarditis with a focus on the more recent available literature.

Using a multiwavelength suite of microwave instruments to investigate the microphysical structure of deep convective cores.

Due to the large natural variability of its microphysical properties, the characterization of solid precipitation is a longstanding problem. Since in situ observations are unavailable in severe convective systems, innovative remote sensing retrievals are needed to extend our understanding of such systems. This study presents a novel technique able to retrieve the density, mass, and effective diameter of graupel and hail in severe convection through the combination of airborne microwave remote sensing instruments. The retrieval is applied to measure solid precipitation properties within two convective cells observed on 23-24 May 2014 over North Carolina during the IPHEx campaign by the NASA ER-2 instrument suite. Between 30 and 40 degrees of freedom of signal are associated with the measurements, which is insufficient to provide full microphysics profiling. The measurements have the largest impact on the retrieval of ice particle sizes, followed by ice water contents. Ice densities are mainly driven by a priori assumptions, though low relative errors in ice densities suggest that in extensive regions of the convective system, only particles with densities larger than 0.4 g/cm3 are compatible with the observations. This is in agreement with reports of large hail on the ground and with hydrometeor classification derived from ground-based polarimetric radars observations. This work confirms that multiple scattering generated by large ice hydrometeors in deep convection is relevant for airborne radar systems already at Ku band. A fortiori, multiple scattering will play a pivotal role in such conditions also for Ku band spaceborne radars (e.g., the GPM Dual Precipitation Radar).

Spatially resolved SO2 flux emissions from Mt Etna.

We report on a systematic record of SO2 flux emissions from individual vents of Etna volcano (Sicily), which we obtained using a permanent UV camera network. Observations were carried out in summer 2014, a period encompassing two eruptive episodes of the New South East Crater (NSEC) and a fissure-fed eruption in the upper Valle del Bove. We demonstrate that our vent-resolved SO2 flux time series allow capturing shifts in activity from one vent to another and contribute to our understanding of Etna's shallow plumbing system structure. We find that the fissure eruption contributed ~50,000 t of SO2 or ~30% of the SO2 emitted by the volcano during the 5 July to 10 August eruptive interval. Activity from this eruptive vent gradually vanished on 10 August, marking a switch of degassing toward the NSEC. Onset of degassing at the NSEC was a precursory to explosive paroxysmal activity on 11-15 August.

Dabrafenib in metastatic melanoma: a monocentric 'real life' experience.

Dabrafenib is a potent BRAF-kinase inhibitor. Its activity was evaluated on 40 consecutive metastatic melanoma patients (pts) harboring the V600BRAF mutations. Dabrafenib was administered orally at the dosage of 150 mg b.i.d. daily. ORR was 82%, with 7% CR, 62% PR, 13% SD and 18% PD. The median PFS and OS were seven and 17 months, respectively (median follow-up: 8.5 months). Increased risk of progression was found in pts with elevated LDH, ECOG PS >1 and more than two metastatic sites. Grade 3-4 adverse events were recorded in 4 pts. In this retrospective analysis, Dabrafenib confirmed its role as the standard clinical option in metastatic melanoma pts.

Early diagnosis of bladder cancer through the detection of urinary tyrosine-phosphorylated proteins.

BACKGROUND: A noninvasive, highly sensitive and specific urine test is needed for bladder cancer (BC) diagnosis and surveillance in addition to the invasive cystoscopy. We previously described the diagnostic effectiveness of urinary tyrosine-phosphorylated proteins (UPY) and a new assay (UPY-A) for their measurement in a pilot study. The aim of this work was to evaluate the performances of the UPY-A using an independent cohort of 262 subjects. METHODS: Urinary tyrosine-phosphorylated proteins were measured by UPY-A test. The area under ROC curve, cutoff, sensitivity, specificity and predictive values of UPY-A were determined. The association of UPY levels with tumour staging, grading, recurrence and progression risk was analysed by Kruskal-Wallis and Wilcoxon's test. To test the probability to be a case if positive at the UPY-A, a logistic test adjusted for possible confounding factor was used. RESULTS: Results showed a significant difference of UPY levels between patients with BC vs healthy controls. For the best cutoff value, 261.26 Standard Units (SU), the sensitivity of the assay was 80.43% and the specificity was 78.82%. A statistically significant difference was found in the levels of UPY at different BC stages and grades between Ta and T1 and with different risk of recurrence and progression. A statistically significant increased risk for BC at UPY-A ⩾261.26 SU was observed. CONCLUSIONS: The present study supplies important information on the diagnostic characteristics of UPY-A revealing remarkable performances for early stages and allowing its potential use for different applications encompassing the screening of high-risk subjects, primary diagnosis and posttreatment surveillance.

Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients.

BACKGROUND: Ipilimumab improves the survival of metastatic melanoma patients. Despite documented, durable objective responses, a significant number of patients fails to benefit from treatment. The aim of this study was to identify an upfront marker for treatment benefit. METHODS: A total of 187 metastatic melanoma patients treated in three Italian Institutions with 3 mg kg(-1) ipilimumab, and 27 patients treated with 10 mg kg(-1) ipilimumab, were evaluated. Neutrophil-to-lymphocyte ratio (NLR) was calculated from pre-therapy full blood counts. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox models were applied, adjusting for confounders and other prognostic factors. RESULTS: In the training cohort of 69 patients treated at European Institute of Oncology, pre-therapy NLR was identified as the strongest and independent marker for treatment benefit in multivariate analyses. Patients with baseline NLR<5 had a significantly improved PFS (HR=0.38; 95% CI: 0.22-0.66; P=0.0006) and OS (HR=0.24; 95% CI: 0.13-0.46; P<0.0001) compared with those with a NLR⩾5. Associations of low NLR with improved survival were confirmed in three validation cohorts of patients. CONCLUSION: Our findings show that baseline NLR is strongly and independently associated with outcome of patients treated with ipilimumab, and may serve to identify patients most likely to benefit from this therapy.

Multiple scattering in observations of the GPM dual-frequency precipitation radar: Evidence and impact on retrievals.

This paper illustrates how multiple scattering signatures affect Global Precipitation Measuring (GPM) Mission Dual-Frequency Precipitation Radar (DPR) Ku and Ka band reflectivity measurements and how they are consistent with prelaunch assessments based on theoretical considerations and confirmed by airborne observations. In particular, in the presence of deep convection, certain characteristics of the dual-wavelength reflectivity profiles cannot be explained with single scattering, whereas they are readily explained by multiple-scattering theory. Examples of such signatures are the absence of surface reflectivity peaks and anomalously small reflectivity slopes in the lower troposphere. These findings are relevant for DPR-based rainfall retrievals and stratiform/convective classification algorithms when dealing with deep convective regions. A path to refining the rainfall inversion problem is proposed by adopting a methodology based on a forward operator which accounts for multiple scattering. A retrieval algorithm based on this methodology is applied to a case study over Africa, and it is compared to the standard DPR products obtained with the at-launch version of the standard algorithms.

Observational study of sleep-related disorders in Italian patients with Parkinson's disease: usefulness of the Italian version of Parkinson's disease sleep scale.

Sleep disturbances are common in patients with Parkinson's disease (PD). We aimed to evaluate prevalence and severity of nighttime sleep disturbances in Italian PD patients and to validate the Italian version of the Parkinson's disease sleep scale. A total of 221 PD patients and 57 healthy controls participated in a cross-sectional study with retest. PDSS, Epworth Sleepiness Scale (ESS), Hamilton Depression Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehn and Yahr staging were applied. PDSS total and individual items scores from patients were significantly lower than those in controls. Internal consistency of PDSS scale was satisfactory and intraclass correlation coefficient for test-retest reliability was 0.96 for total PDSS score. A significant negative correlation was found between total PDSS and ESS scores, and between total PDSS and HDRS scores. PDSS scores were also related to UPDRS sections II, III and IV, and H&Y stage. PDSS and ESS scores were not related to levodopa equivalent dose. Daytime sleepiness, depressive symptoms and disease severity correlate with sleep disturbances in Italian PD patients. The PDSS is a valid and reliable tool to evaluate sleep disturbances in Italian patients.

Identification of a serum-detectable metabolomic fingerprint potentially correlated with the presence of micrometastatic disease in early breast cancer patients at varying risks of disease relapse by traditional prognostic methods.

BACKGROUND: Prognostic tools in early breast cancer are inadequate. The evolving field of metabolomics may allow more accurate identification of patients with residual micrometastases. PATIENTS AND METHODS: Forty-four early breast cancer patients with pre- and postoperative serum samples had metabolomic assessment by nuclear magnetic resonance. Fifty-one metastatic patients served as control. Differential clustering was identified and used to calculate individual early patient 'metabolomic risk', calculated as inverse distance of each early patient from the metastatic cluster barycenter. Metabolomic risk was compared with Adjuvantionline 10-year mortality assessment. RESULTS: Innate serum metabolomic differences exist between early and metastatic patients. Preoperative patients were identified with 75% sensitivity, 69% specificity and 72% predictive accuracy. Comparison with Adjuvantionline revealed discordance. Of 21 patients assessed as high risk by Adjuvantionline, 10 (48%) and 6 (29%) were at high risk by metabolomics in pre- and postoperative settings, respectively. Of 23 low-risk patients by Adjuvantionline, 11 (48%) preoperative and 20 (87%) postoperative patients were at low risk by metabolomics. CONCLUSIONS: This study identifies metabolomic discrimination between early and metastatic breast cancer. Micrometastatic disease may account for metabolomic misclassification of some early patients as metastatic. Metabolomics identifies more patients as low relapse risk compared with Adjuvantionline. Further exploration of this metabolomic fingerprint is warranted.

The Bass technique using a specially designed toothbrush.

BACKGROUND: Reducing the plaque index (PI) is still the main objective in the prevention of gingivitis and periodontitis. AIM: This experiment evaluated the efficiency of a new manual toothbrush shape from two perspectives: allowing the maximum exploitation of the bristle surface in all directions of the dental arches and simplifying the Bass technique handling and movements in domestic oral care. PATIENTS AND METHOD: The distinct shape was obtained by distancing the bristle surface from the surface of the toothbrush handle in the direction of the bristles, maintaining the two surfaces on parallel planes. This modification facilitates brushing with the Bass technique, since rotation of the new toothbrush handle on its axis allows the bristle surface to cover a greater area. Sixteen patients between the ages of 23 and 49 years with at least 28 dental elements were divided randomly into two groups. On the first day, they underwent professional plaque removal and were provided with pairs of toothbrushes to test. They were evaluated 30 days later using the Full Mouth Plaque Score determined by two dental hygienists who were unaware of the instructions given concerning the method, quadrants and toothbrushes used for the experiment. RESULTS: The results showed that the modifications to the manual toothbrushes produced greater PI control compared with the traditionally shaped toothbrushes. CONCLUSION: Although oral hygiene testing at home usually provides subjective information, in this experiment, the data provided a positive, objective result.

EphrinB2 induces tyrosine phosphorylation of NR2B via Src-family kinases during inflammatory hyperalgesia.

In recent years a role for EphB receptor tyrosine kinases and their ephrinB ligands in activity-dependent synaptic plasticity in the CNS has been identified. The aim of the present study was to test the hypothesis that EphB receptor activation in the adult rat spinal cord is involved in synaptic plasticity and processing of nociceptive inputs, through modulation of the function of the glutamate ionotropic receptor NMDA (N-methyl-D-aspartate). In particular, EphB receptor activation would induce phosphorylation of the NR2B subunit of the NMDA receptor by a Src family non-receptor tyrosine kinase. Intrathecal administration of ephrinB2-Fc in adult rats, which can bind to and activate EphB receptors and induce behavioral thermal hyperalgesia, led to NR2B tyrosine phosphorylation, which could be blocked by the Src family kinase inhibitor PP2. Furthermore animals pre-treated with PP2 did not develop behavioral thermal hyperalgesia following EphrinB2-Fc administration, suggesting that this pathway is functionally significant. Indeed, EphB1-Fc administration, which competes with the endogenous receptor for ephrinB2 binding and prevents behavioral allodynia and hyperalgesia in the carrageenan model of inflammation, also inhibited NR2B phosphorylation in this model. Taken together these findings support the hypothesis that EphB-ephrinB interactions play an important role in NMDA-dependent, activity-dependent synaptic plasticity in the adult spinal cord, inducing the phosphorylation of the NR2B subunit of the receptor via Src family kinases, thus contributing to chronic pain states.

Subtelomeric analysis detects a familial 10p;12p rearrangement in two relatives with a distinct syndrome.

In recent years, subtelomeric rearrangements have been identified as a major cause of multiple congenital anomalies (MCA)/mental retardation (MR) syndromes. Currently, more than 2,500 individuals with MR have been tested and subtelomeric rearrangements were detected in about 6%. Therefore, subtelomeric FISH analysis is indicated as a second tier test after high-resolution G-banding analysis, in subjects with otherwise unexplained developmental delay/MR and/or MCA. We describe a female patient and her maternal aunt, both showing a distinct phenotype, associated with the same complex subtelomeric rearrangement. Subtelomeric FISH testing performed between 1 year 9 months and 20 years after the initial karyotype showed, in both patients, distal trisomy 12p and distal monosomy 10p as follows: 46,XX.ish der(10)t(10;12)(p15.3;p13.31). Parental subtelomeric FISH analysis showed the proposita's mother (sister of Patient 2) and grandmother (mother to Patient 2), to have a balanced 10p:12p translocation. Both girls showed a similar phenotype with pre/postnatal growth retardation, moderate-to-severe developmental delay/MR, very poor/absent speech, hypotonia, lax ligaments, and a distinct pattern of malformation. On examination there were blepharophimosis; bilateral ptosis/epicanthus; broad, depressed nasal bridge with a beaked nose; short philtrum; low-set, posteriorly rotated, overfolded ears; micrognathia; mild webbing of the neck; mild broadening of thumbs; puffy hands/feet; long hallux; and sacral/coccygeal dimples. A slow overall improvement was seen in both patients over time. To our knowledge, a complex subtle rearrangement as the one seen in our patients has not been reported thus far. Our patients show features of partial 10p deletion syndrome rather than those of partial duplication 12p, confirming the general rule that deletions are more phenotypically penetrant than duplications.