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The Superconducting Ion Gantry (SIG) project aims to design, construct, and test a curved superconducting dipole demonstrator magnet for an ion gantry (up to a rigidity of 6.6 Tm). The main demonstrator magnet parameters are a dipolar field of 4 T generated into a toroidal aperture with an 80 mm diameter, 1.65 m curvature radius, and 30° angular sector. The project is inserted in the framework of the EuroSIG collaboration among CNAO, CERN, INFN, and MedAustron. Within this collaboration, the main goal of SIG is to perform a feasibility study of winding and assembling cos-$\theta$ coils with a small curvature radius. In addition, a parallel program at CERN is dedicated to the study of the indirect cooling problem through the construction of a straight thermal demonstrator magnet sharing the SIG cross-section. The basic idea behind these programs is to check whether the vast experience of the community on superconducting accelerator magnets design can lead to a breakthrough in the gantry magnets domain. This article shows the main elements of the conceptual design of the SIG magnet and reports on the first winding trial performed at the LASA laboratory, in Milan, with a copper dummy cable. Moreover, possible solutions for the winding, curing, and impregnation of highly curved cos$\theta$ coils are discussed.

The use of Canted Cosine Theta (CCT) magnets for accelerator applications has gained popularity due to their ease of manufacturing and assembly. In the context of two EU-Horizon2020-funded projects, HITRIplus and IFAST, the development of two 80 mm free bore and 4 T central field CCT dipoles for use in ion therapy (hadron therapy) is underway. In IFAST, a straight dipole CCT features a superimposed quadrupole component (combined function winding), while in HITRIplus a curved CCT (bending radius of 1.65 m) is wound as pure dipole. Both projects are based on a Cu/Nb-Ti multistrand rope as conductor. The article presents advancements in the engineering design of the magnets. A number of validation tests have been made to validate the choices made during the conceptual design. Characterization tests of the low losses rope, winding tests, splice tests, and impregnation tests will be described. The explored alternatives for the fabrication of the curved formers and the support structure are also discussed.

This study aims to evaluate the advantages and criticalities of applying additive manufacturing to produce climbing holds replicating real rocky surfaces. A sample of a rocky surface has been reproduced with a budget-friendly 3D scanner exploiting structured light and made in additive manufacturing. The methodology is designed to build a high-fidelity replica of the rocky surface using only minor geometry modifications to convert a 2D triangulated surface into a 3D watertight model optimised for additive manufacturing. In addition, the research uses a novel design and uncertainty estimation approach. The proposed methodology proved capable of replicating a rocky sample with sub-millimetre accuracy, which is more realistic than conventional screw-on plastic holds currently used in climbing gyms. The advantages can be addressed in terms of customisation, manufacturing cost and time reduction that could lead to real outdoor climbing experiences in indoor environments by coupling additive manufacturing techniques and reverse engineering (RE). However, operating the scanner in a rocky environment and the considerable size of the climbing routes suggest that further research is needed to extend the proposed methodology to real case studies. Further analysis should focus on selecting the best material and additive manufacturing technology to produce structural components for climbing environments.

This paper addresses electromagnetic losses in Canted-Cosine-Theta (CCT) magnets, especially relevant for fast-ramped, conduction-cooled CCTs in hadron therapy. It discusses losses in metallic formers, using both analytical models and FEM simulations. It then addresses losses in multifilamentary superconductors under AC fields, accounting for persistent and interfilament losses under longitudinal and transversal field with a 3D Volume Integral Method. As a closing example, losses of the LTS (Nb-Ti) CCT dipole designed in HITRIplus and I.FAST collaborations are computed.

Canted Cosine Theta layout for accelerator magnets is a very attractive since such magnets can be manufactured and assembled without big tooling, and with a relatively modest number of parts and tools. In the frame of European Horizon2020 funds, two collaborations, HITRIplus and I.FAST, are developing a CCT design, of 80 mm free bore, 4 T central dipole field, and 0.4 T/s ramp-rate. This magnet is expected to be the bending element of a gantry, to control the beam delivery in therapy with ions (hadrontherapy). The paper illustrates first a comparison between CCT and more classical cosine theta layout, followed by the comparison between Nb-Ti, Nb3Sn, MgB2, and HTS tapes coils. Relevant requirement for the magnets of this study is to be operated at low current, to limit the heat generation, in sight of a liquid-free cooling system. The results of the comparison is then applied to the design of two magnet demonstrators. Both adopt a low-losses Nb-Ti rope, consistently with the need for keeping the heat generation as low as possible. The first is a straight combined function dipole-quadrupole, while the second is a curved CCT dipole. The paper concludes with the first manufacturing tests for the CCT formers, for which aluminium -bronze, stainless steel and charged PEEK polymer are being explored as basic material.

Purpose To study the post-operative refractive error (RE) of patients undergoing combined phaco-vitrectomy and to find out which intraocular lens (IOL)-power formula had the best refractive outcomes.Methods In this retrospective multicentric study we compared the preoperative expected target with the postoperative RE of patients undergoing combined phaco-vitrectomy due to vitreomacular traction, macular pucker, full thickness macular hole or lamellar macular hole. A multinomial logistic regression was performed to compare the postoperative REs and the differences between expected and postoperative REs among the SRK-T, Olsen's and Holladay-2 formulas. The correlation between the difference in REs and IOL-power was also studied.Results Sixty-seven eyes with a mean axial length of 23.73 ± 1.21 mm were included. Forty-two (63%), 14 (21%) and 11 (16%) eyes were implanted with an IOL that was calculated respectively with SRK-T, Olsen's and the Holladay-2 formula. The mean preoperative expected- and post-operative REs were −0.16 ± 0.12D and −0.48 ± 0.17, respectively (p= 0.045). SRK-T and Holladay-2 formulas led to a significant myopic shift whereas Olsen's caused a significant hyperopic error, independently from the IOL power.Conclusion Independently from the IOL power, none of the analyzed formulas is precise at calculating the post-operative RE.

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Like all surgeries, penile prosthesis implantation (PPI) has the potential for both postoperative complications and suboptimal patient satisfaction. In order to assess risk factors for poor satisfaction, we reviewed patients who had been prospectively recruited in a national multi-institutional registry of penile prostheses procedures (INSIST-ED) from 2014 to 20121. Patient baseline characteristics and postoperative complications were recorded. The primary endpoint of this study was unfavorable outcomes after inflatable PPI, defined as significant postoperative complications (Clavien–Dindo ≥2) and/or Sexuality with Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) scores below the 10th percentile. A total of 256 patients were included in the study. The median age was 60 years (IQR 56–67). The most common cause of erectile dysfunction (ED) was organic (42.2%), followed by pelvic surgery/radiotherapy (39.8%) and Peyronie’s disease (18.0%). Postoperative complications were recorded in 9.6%. High-grade complications (Clavien ≥2) occurred in 4.7%. At 1-year follow-up, the median QoLSPP total score was 71 (IQR 65–76). In all, 14.8% of patients were classified as having experienced unfavorable outcomes because of significant postoperative complications and/or QoLSPP scores below the 10th percentile. Logistic regression analysis demonstrated patient age to be non-linearly associated with the risk of experiencing unfavorable outcomes. A U-shaped correlation showed a lower risk for younger and older patients and a higher risk for middle-aged men. ED etiology and surgical volume were not associated with PPI outcomes. Physicians should, therefore, be aware that middle-aged men may be at higher risk of being unsatisfied following PPI compared to both younger and older patients.

Dynamical low-rank approximation has become a valuable tool to perform an on-the-fly model order reduction for prohibitively large matrix differential equations. A core ingredient is the construction of integrators that are robust to the presence of small singular values and the resulting large time derivatives of the orthogonal factors in the low-rank matrix representation. Recently, the robust basis-update & Galerkin (BUG) class of integrators has been introduced. These methods require no steps that evolve the solution backward in time, often have favourable structure-preserving properties, and allow for parallel time-updates of the low-rank factors. The BUG framework is flexible enough to allow for adaptations to these and further requirements. However, the BUG methods presented so far have only first-order robust error bounds. This work proposes a second-order BUG integrator for dynamical low-rank approximation based on the midpoint quadrature rule. The integrator first performs a half-step with a first-order BUG integrator, followed by a Galerkin update with a suitably augmented basis. We prove a robust second-order error bound which in addition shows an improved dependence on the normal component of the vector field. These rigorous results are illustrated and complemented by a number of numerical experiments.

In algorithms for solving optimization problems constrained to a smooth manifold, retractions are a well-established tool to ensure that the iterates stay on the manifold. More recently, it has been demonstrated that retractions are a useful concept for other computational tasks on manifold as well, including interpolation tasks. In this work, we consider the application of retractions to the numerical integration of differential equations on fixed-rank matrix manifolds. This is closely related to dynamical low-rank approximation (DLRA) techniques. In fact, any retraction leads to a numerical integrator and, vice versa, certain DLRA techniques bear a direct relation with retractions. As an example for the latter, we introduce a new retraction, called KLS retraction, that is derived from the so-called unconventional integrator for DLRA. We also illustrate how retractions can be used to recover known DLRA techniques and to design new ones. In particular, this work introduces two novel numerical integration schemes that apply to differential equations on general manifolds: the accelerated forward Euler (AFE) method and the Projected Ralston–Hermite (PRH) method. Both methods build on retractions by using them as a tool for approximating curves on manifolds. The two methods are proven to have local truncation error of order three. Numerical experiments on classical DLRA examples highlight the advantages and shortcomings of these new methods.

The interest of industrial companies for the Additive Manufacturing (AM) technology is growing year after year due to its capability of producing components with complex shapes that fit industrial engineering necessities better than traditionally manufactured parts. However, conventional Computer-Aided Design (CAD) software are often limited for the design and representation of complex geometries, especially when dealing with lattice structures: these are bio-inspired structures composed of repeated small elements, called struts, which are combined to shape a unit cell that is repeated across a domain. This design method generates a lightweight but stiff component. The scope of this work is to analyse the problem of the lattice structures representation in 2 D technical drawings and propose some contributions to support the development of Standards for their 2 D representation. This work is focused on the proposal of rules useful to represent such hierarchic structures. Python language and the open-source software FreeCad™ are used as a software platform to evaluate the suitability and usability of the proposed representation standard. This is based on simplified symbols to describe complex lattice structures instead of representing all the elements which constitute the lattice. The standard is thought to be used in technical 2 D drawings where assemblies are represented and lattice components are used (e.g. parts assembly, maintenance, parts catalogues). A case study is included to describe how the proposed standard could be integrated into a 2 D assembly drawing, following technical product documentation production typical workflow.

We propose and analyse a numerical integrator that computes a low-rank approximation to large time-dependent matrices that are either given explicitly via their increments or are the unknown solution to a matrix differential equation. Furthermore, the integrator is extended to the approximation of time-dependent tensors by Tucker tensors of fixed multilinear rank. The proposed low-rank integrator is different from the known projector-splitting integrator for dynamical low-rank approximation, but it retains the important robustness to small singular values that has so far been known only for the projector-splitting integrator. The new integrator also offers some potential advantages over the projector-splitting integrator: It avoids the backward time integration substep of the projector-splitting integrator, which is a potentially unstable substep for dissipative problems. It offers more parallelism, and it preserves symmetry or anti-symmetry of the matrix or tensor when the differential equation does. Numerical experiments illustrate the behaviour of the proposed integrator.

A rank-adaptive integrator for the dynamical low-rank approximation of matrix and tensor differential equations is presented. The fixed-rank integrator recently proposed by two of the authors is extended to allow for an adaptive choice of the rank, using subspaces that are generated by the integrator itself. The integrator first updates the evolving bases and then does a Galerkin step in the subspace generated by both the new and old bases, which is followed by rank truncation to a given tolerance. It is shown that the adaptive low-rank integrator retains the exactness, robustness and symmetry-preserving properties of the previously proposed fixed-rank integrator. Beyond that, up to the truncation tolerance, the rank-adaptive integrator preserves the norm when the differential equation does, it preserves the energy for Schrödinger equations and Hamiltonian systems, and it preserves the monotonic decrease of the functional in gradient flows. Numerical experiments illustrate the behaviour of the rank-adaptive integrator.

Purpose: To evaluate the safety and efficacy of double compared to single intraluminal suture stenting in reducing early postoperative hypertensive spikes (HS) and hypotony after Baerveldt glaucoma implant surgery.Methods: For this retrospective study, we reviewed the medical charts of 60 patients (60 eyes) who underwent Baerveldt drainage device surgery between 2017 and 2019. Two groups were formed according to whether a single suture stent was placed within the tube (5-0 polypropylene, 30 eyes, group 1) or a double suture (5-0 and 6-0 polypropylene, 30 eyes, group 2). Intraocular pressure (IOP) was measured at baseline, at 6 h, and on postoperative days 1, 2, 5, 7, 14, 21, 30, 60, 90, 180. The occurrence of HS (IOP ⩾ 30 mmHg), anterior chamber reformation, decompressive paracentesis, anti-glaucoma medication, and adverse events were recorded.Results: There was a greater decrease in IOP from baseline at days 1, 2, and 21 (p< 0.05) and number of HS at 6 h (p= 0.006) and postoperative day 1 (p< 0.001) in group 2. The mean number of decompressive paracentesis, anterior chamber reformation procedures, and topical anti-glaucoma medications was the same in both groups; the need for oral acetazolamide was significantly lower in group 2 at days 1, 21, and 30 (p< 0.05).Conclusions: While both stenting methods provide a gradual, controlled decrease in IOP, the double stenting technique was associated with a sooner and greater postoperative reduction in IOP and a good safety profile thanks to fewer HS in the early postoperative period and less need for oral acetazolamide.

Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care.

Nowadays additive manufacturing is affected by a rapid expansion of possible applications. It is defined as a set of technologies that allow the production of components from 3D digital models in a short time by adding material layer by layer. It shows enormous potential to support wind musical instruments manufacturing because the design of complex shapes could produce unexplored and unconventional sounds, together with external customization capabilities. The change in the production process, material and shape could affect the resulting sound. This work aims to compare the music performances of 3D-printed trombone mouthpieces using both Fused Deposition Modelling and Stereolithography techniques, compared to the commercial brass one. The quantitative comparison is made applying a Design of Experiment methodology, to detect the main additive manufacturing parameters that affect the sound quality. Digital audio processing techniques, such as spectral analysis, cross-correlation and psychoacoustic analysis in terms of loudness, roughness and fluctuation strength have been applied to evaluate sounds. The methodology herein applied could be used as a standard for future studies on additively manufactured musical instruments.

Previous studies have shown discrepancies among countries in terms of treatment indications and patients’ management due to different health care policies. Penile prosthesis implantation (PPI) is a highly effective treatment for erectile dysfunction (ED), which may have different accessibility according to the type of health system. We compared clinical characteristics of patients included in two national registries on PPI to investigate the influence of different health care systems on treatment indication and accessibility. The multicenter Italian Nationwide Systematic Inventarization of Surgical Treatment for ED (INSIST-ED) Registry and the multicenter Prospective Registry of Outcomes with Penile Prosthesis for Erectile Restoration (PROPPER), respectively for Italy and North America were considered. Clinical characteristics of patients included in both registries were compared using Wilcoxon Rank Sum test and the Pearson’s Chi square test. Patients submitted to PPI in Italy are significantly younger (age: 61.2 vs. 63.8 years; p≤ 0.001) compared with North America. The majority of patients are treated for post-radical prostatectomy ED in both registries (Italy: 31%; North America: 27%), although diabetes and cardiovascular diseases are more frequent reasons for PPI in the PROPPER registry (p≤ 0.001), reflecting differences in disease prevalence among countries. In North America a non-hydraulic implant is considered only in 1% of cases as compared with 3% in Italy (p≤ 0.001). In terms of postoperative management, a compressive surgical dressing (98% vs. 24%; p≤ 0.001) is a more common strategy in North America. Finally, in Italy most surgeries are performed in a public hospital (82%), while the private setting (70.8%) is more common in North America (p≤ 0.001). These findings suggest differences in health care systems between Italy and North America. A system like the American one would guarantee easier access to PPI in countries where the National Health System is mainly based on reimbursement to public hospital settings and where patients choosing private settings have to pay by themselves.

This is the first case report of a patient with ALK-rearranged metastatic lung adenocarcinoma who became pregnant during treatment with alectinib. A multidisciplinary team of gynecologists, neonatologists, oncologists, psychologists, and pharmacologists was set up to handle the case. According to patient’s preference, the study drug was continued throughout pregnancy and the woman delivered a healthy baby girl at 35 weeks and 5 days of gestation. Fetal parameters remained normal during pregnancy. At birth, alectinib levels were 14 times higher in maternal plasma than in the fetus (259 versus 18 ng/mL). The average concentration of alectinib in the placenta was 562 ng/g. The baby was followed during her first 20 months, and no developmental anomalies were observed. After 32 months from diagnosis, the mother is well and in partial remission.

Microdissection testicular sperm extraction (mTESE) has been proposed as a salvage treatment option for men with a previously failed classic TESE (cTESE), but data are scarce. We aimed to assess the outcome of and potential predictors of successful salvage mTESE in a cohort of men previously submitted to unfruitful cTESE. Data from 61 men who underwent mTESE after a failed cTESE between 01/2014 and 10/2020, at 6 tertiary-referral centres in Italy were analysed. All men were investigated with semen analyses, testicular ultrasound, hormonal and genetic blood testing. Pathological diagnosis from TESE was collected in every man. Descriptive statistics and logistic regression models were used to investigate potential predictors of positive sperm retrieval (SR+) after salvage mTESE. Baseline serum Follicle-Stimulating hormone (FSH) and total testosterone levels were 17.2 (8.6–30.1) mUI/mL and 4.7 (3.5-6.4) ng/mL, respectively. Sertoli-cell-only syndrome (SCOS), maturation arrest (MA) and hypospermatogenesis were found in 24 (39.3%), 21 (34.4%) and 16 (26.2%) men after cTESE, respectively. At mTESE, SR+ was found in 30 (49.2%) men. Patients with a diagnosis of hypospermatogenesis had a higher rate of SR+ (12/16 (75%)) compared to MA (12/21 (57.1%)) and SCOS (6/24 (25%)) patients at mTESE (p< 0.01). No clinical and laboratory differences were observed between SR+ and SR- patients at mTESE. There were no significant complications after mTESE. At multivariable logistic regression analysis, only hypospermatogenesis (OR 9.5; p< 0.01) was independently associated with SR+ at mTESE, after accounting for age and FSH.

Within the final steps of lithium-ion battery production, the electrolyte wetting, and formation are decisive for long and safe battery operation. In addition to the extensive process times of these production steps, the throughput times are extended to ensure that the required product quality is reached. This paper presents a conceptual smart production system that pursues lean production by linking multiple process steps, thus decreasing the transportation and idle times. Cell quality can be determined in real-time by using innovative measuring techniques as inline detection methods for the process and product state. Furthermore, a cyber-physical system that analyzes the battery quality and controls the process flow for each cell individually is presented.

La télémédecine est en plein essor dans tous les domaines médicaux. En plus d’être l’une des priorités de l’OMS afin de répondre aux problèmes des coûts et de l’accessibilité à des soins de qualité, que ce soit dans les pays développés ou en voie de développement, la crise sanitaire récente liée au COVID-19 a montré qu’elle pouvait être un atout certain pour la permanence des soins en situation de crise. Si la télémédecine en anesthésie se développe pour l’ensemble de la prise en charge péri-opératoire des patients, cette mise au point vise à présenter les données récentes de la littérature concernant la place de la télémédecine en anesthésie pour l’évaluation pré-opératoire. Quatre points principaux sont abordés : (1) l’éligibilité et la faisabilité de la téléconsultation d’anesthésie; (2) son efficacité en terme de temps passé en consultation d’anesthésie, taux d’annulation d’intervention et concordance de l’examen physique; (3) la satisfaction des patients, et enfin; (4) son potentiel impact économique.

Metabolic reprogramming is emerging as a cancer vulnerability that could be therapeutically exploitable using different approaches, including amino acid depletion for those tumors that rely on exogenous amino acids for their maintenance. ʟ-Asparaginase (ASNase) has contributed to a significant improvement in acute lymphoblastic leukemia outcomes; however, toxicity and resistance limit its clinical use in other tumors. Here, we report that, in multiple myeloma (MM) cells, the DNA methylation status is significantly associated with reduced expression of ASNase-related gene signatures, thus suggesting ASNase sensitivity for this tumor. Therefore, we tested the effects of ASNase purified from Erwinia chrysanthemi (Erw-ASNase), combined with the next-generation proteasome inhibitor (PI) carfilzomib. We observed an impressive synergistic effect on MM cells, whereas normal peripheral blood mononuclear cells were not affected. Importantly, this effect was associated with increased reactive oxygen species (ROS) generation, compounded mitochondrial damage, and Nrf2 upregulation, regardless of the c-Myc oncogenic-specific program. Furthermore, the cotreatment resulted in genomic instability and DNA repair mechanism impairment via increased mitochondrial oxidative stress, which further enhanced its antitumor activity. Interestingly, carfilzomib-resistant cells were found to be highly dependent on amino acid starvation, as reflected by their higher sensitivity to Erw-ASNase treatment compared with isogenic cells. Overall, by affecting several cellular programs, Erw-ASNase makes MM cells more vulnerable to carfilzomib, providing proof of concept for clinical use of this combination as a novel strategy to enhance PI sensitivity in MM patients.

Metabolic reprogramming is emerging as a cancer vulnerability that could be therapeutically exploitable using different approaches, including amino acid depletion for those tumors that rely on exogenous amino acids for their maintenance. ʟ-Asparaginase (ASNase) has contributed to a significant improvement in acute lymphoblastic leukemia outcomes; however, toxicity and resistance limit its clinical use in other tumors. Here, we report that, in multiple myeloma (MM) cells, the DNA methylation status is significantly associated with reduced expression of ASNase-related gene signatures, thus suggesting ASNase sensitivity for this tumor. Therefore, we tested the effects of ASNase purified from Erwinia chrysanthemi(Erw-ASNase), combined with the next-generation proteasome inhibitor (PI) carfilzomib. We observed an impressive synergistic effect on MM cells, whereas normal peripheral blood mononuclear cells were not affected. Importantly, this effect was associated with increased reactive oxygen species (ROS) generation, compounded mitochondrial damage, and Nrf2 upregulation, regardless of the c-Myc oncogenic-specific program. Furthermore, the cotreatment resulted in genomic instability and DNA repair mechanism impairment via increased mitochondrial oxidative stress, which further enhanced its antitumor activity. Interestingly, carfilzomib-resistant cells were found to be highly dependent on amino acid starvation, as reflected by their higher sensitivity to Erw-ASNase treatment compared with isogenic cells. Overall, by affecting several cellular programs, Erw-ASNase makes MM cells more vulnerable to carfilzomib, providing proof of concept for clinical use of this combination as a novel strategy to enhance PI sensitivity in MM patients.

A numerical integrator is presented that computes a symmetric or skew-symmetric low-rank approximation to large symmetric or skew-symmetric time-dependent matrices that are either given explicitly or are the unknown solution to a matrix differential equation. A related algorithm is given for the approximation of symmetric or anti-symmetric time-dependent tensors by symmetric or anti-symmetric Tucker tensors of low multilinear rank. The proposed symmetric or anti-symmetric low-rank integrator is different from recently proposed projector-splitting integrators for dynamical low-rank approximation, which do not preserve symmetry or anti-symmetry. However, it is shown that the (anti-)symmetric low-rank integrators retain favourable properties of the projector-splitting integrators: given low-rank time-dependent matrices and tensors are reproduced exactly, and the error behaviour is robust to the presence of small singular values, in contrast to standard integration methods applied to the differential equations of dynamical low-rank approximation. Numerical experiments illustrate the behaviour of the proposed integrators.

Supplemental Digital Content is available in the text.

Purpose: To evaluate if jugular vein flow restoration in various venographic defects indicative of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) patients can have positive effects on cerebral lesions identified using magnetic resonance imaging (MRI).Materials and Methods: The Brave Dreams trial (ClinicalTrials.govidentifier NCT01371760) was a multicenter, randomized, parallel group, double-blind, sham-controlled trial to assess the efficacy of jugular venoplasty in MS patients with CCSVI. Between August 2012 and March 2016, 130 patients (mean age 39.9±10.6 years; 81 women) with relapsing/remitting (n=115) or secondary/progressive (n=15) MS were randomized 2:1 to venography plus angioplasty (n=86) or venography (sham; n=44). Patients and study personnel (except the interventionist) were masked to treatment assignment. MRI data acquired at 6 and 12 months after randomization were compared to the preoperative scan for new and/or >30% enlargement of T2 lesions plus new gadolinium enhancement of pre-existing lesions. The relative risks (RR) with 95% confidence interval (CI) were estimated and compared. In a post hoc assessment, venograms of patients who underwent venous angioplasty were graded as “favorable” (n=38) or “unfavorable” (n=30) for dilation according to the Giaquinta grading system by 4 investigators blinded to outcomes. These subgroups were also compared.Results: Of the 130 patients enrolled, 125 (96%) completed the 12-month MRI follow-up. Analysis showed that the likelihood of being free of new cerebral lesions at 1 year was significantly higher after venoplasty compared to the sham group (RR 1.42, 95% CI 1.00 to 2.01, p=0.032). Patients with favorable venograms had a significantly higher probability of being free of new cerebral lesions than patients with unfavorable venograms (RR 1.82, 95% CI 1.17 to 2.83, p=0.005) or patients in the sham arm (RR 1.66, 95% CI 1.16 to 2.37, p=0.005).Conclusion: Expanded analysis of the Brave Dreams data that included secondary/progressive MS patients in addition to the relapsing/remitting patients analyzed previously showed that venoplasty decreases new cerebral lesions at 1 year. Post hoc analysis confirmed the efficacy of the Giaquinta grading system in selecting patients appropriate for venoplasty who were more likely to be free from accumulation of new cerebral lesions at MRI.

There is limited scientific literature regarding the management outcomes for end-stage erectile dysfunction (ED) following radical cystoprostatectomy (RCP). This study aims to evaluate the surgical outcomes of penile prosthesis (PP) implantation. A retrospective analysis over 17 years (2004–2017) was performed from the clinical records of patients in four tertiary referral centres, whom previously had undergone RCP, followed by PP implantation for end-stage ED. Outcome measures include both intra and postoperative complications, operative duration, a 5-point Likert hematoma scale as well as length of hospital stay. Additionally, a matched-pair cohort analysis was performed, dividing patients in 2 groups according to the type of urinary diversion (neobladder versus ileal conduit/cutaneous ureterostomy). The median time elapsed between RCP and PP implantation was 38 months (IQR 20–56). The median follow-up was 18 months (IQR 12–156). A 3-piece inflatable PP was implanted in 43 patients (91.5%) whereas a semirigid device was implanted in the remainder. Reservoir position was extra-peritoneal (utilising a separate abdominal incision) in 24 patients (54.8%), while an ectopic high-submuscular placement was preferred in the remainder. PP infection and mechanical failure occurred in 1 (2.1%) and 3 cases (6.3%) respectively. The comparative analysis of surgical outcomes did not show any statistically significant difference between the two groups. Our evidence suggests that PP implantation in patients with refractory ED following RCP may represent a safe and effective procedure associated with a low incidence of complications. The main limitation of this study is represented by the non-randomised, retrospective nature as well as the lack of patients’ functional outcomes and the limited follow-up.

Introduction To describe the results of iStent injectimplantation as a standalone procedure in early-stage uncontrolled glaucoma, with results up to 24 months.Methods A retrospective, single-center case series that recruited patients with open-angle glaucoma (OAG), uncontrolled IOP (defined as ≥18 mmHg), and who are receiving 1–4 glaucoma medications were implanted the iStent injectas a standalone procedure. Exclusion criteria were the contraindications of iStent injectimplantation. Primary outcome measures were IOP at 6, 12, 18, and 24 months compared to baseline, and the number of medications at baseline and 24 months.Results Eighty-eight eyes from 88 patients, aged 57.6 ± 9.8 years, were included. Ten eyes underwent a subsequent glaucoma procedure during follow-up and were excluded from the analysis. The mean IOP (mmHg) was reduced from 20.54 ± 1.42 at baseline to 15.99 ± 1.98 and 16.15 ± 2.21 (n = 78, p < 0.001) at the 12- and 24-month follow-up, respectively, and the mean number of medications was reduced from 2.35 ± 0.70 to 1.31 ± 0.80 (p < 0.001) at 24 months. Of those eyes, 59% had ≥20% reduction in IOP at 24 months, 91% had an IOP ≤18 mmHg at 24 months, and 71.8% were receiving fewer medications. At 24 months, 14.1% of eyes were medication-free, compared to none at baseline. No serious intraoperative or postoperative adverse events occurred.Discussion iStent injectcan effectively control intraocular pressure in mild glaucoma, reducing medication reliance and improving patient quality of life.

Varicocele is defined as a state of varicosity and tortuosity of the pampiniform plexus around the testis caused by retrograde blood flow through the internal spermatic vein. The prevalence of clinically relevant varicocele ranges from 5 to 20% in the male population and is often associated with infertility and reduction of sperm quality. In this review, the pathophysiology and clinical aspects of varicocele are reviewed along with therapeutic options and treatment effects on sperm parameters and fertility both in adult and in pediatric/adolescent subjects. We conducted a Medline and a PubMed search from 1965 to 2018 to identify publications related to varicocele clinical aspects, treatment procedures and treatment outcomes. Keywords used for the search were: “varicocele”, “varicocelectomy”, “sclerotherapy”, “male infertility”, “subfertility”, and “semen abnormalities”. Data from a large number of studies in adolescent and adult males indicate that varicocele correction improves semen parameters in the majority of patients, reducing oxidative stress and improving sperm nuclear DNA integrity either with surgical or percutaneous approach. Varicocele repair seems to represent a cost-effective therapeutic option for all males (both adolescent and adults) with a clinical varicocele in the presence of testicular hypotrophy, worsening sperm alterations or infertility. On the other hand, some investigators questioned the role of varicocelectomy in the era of assisted reproduction. Thus, a better understanding of the pathophysiology of varicocele-associated male subfertility is of paramount importance to elucidating the deleterious effects of varicocele on spermatogenesis and possibly formulating new treatment strategies.

Background: One of the directions of modern ophthalmology is toward an odontoiatric model, and new settings of eye care are becoming the standard of care: one day surgery and also office-based therapies.Methods: Retrospective analysis of three tertiary-care centers in Italy and analysis of the literature.Results: We provide readers with state-of-the-art measures of prophylaxis in ophthalmic surgery.Discussion and conclusion: Role of antibiotics is criticized in the light of stewardship antimicrobial paradigm.

The purinergic system is composed of purine and pyrimidine transmitters, the enzymes that modulate the interconversion of nucleotides and nucleosides, the membrane transporters that control their extracellular concentrations, and the many receptor subtypes that are responsible for their cellular responses. The components of this system are ubiquitously localized in all tissues and organs, and their involvement in several physiological conditions has been clearly demonstrated. Moreover, extracellular purine and pyrimidine concentrations rise several folds under pathological conditions like tissue damage, ischemia, and inflammation, which suggest that this signaling system might contribute both to disease outcome and, possibly, to its tentative resolution. The complexity of this system has greatly impaired the clear identification of the mediators and receptors that are actually involved in a given pathology, also due to the often opposite roles played by the various receptor subtypes. Nevertheless, this knowledge is fundamental for the possible exploitation of these molecular entities as targets for the development of new pharmacological approaches. In this review, we aim at highlighting what is currently known on the role of the purinergic system in various pain conditions and during inflammatory processes. Although some confusion may arise from conflicting results, literature data clearly show that targeting specific purinergic receptors may represent an innovative approach to various pain and inflammatory conditions, and that new purine-based drugs are now very close to reach the market with these indications.

This paper offers a summary of several years of high altitude archaeological investigations that I have undertaken in the South American Andes, focusing on the strategies used by the Inca civilization to choose Andean peaks for the construction of mountaintop shrines that are the highest archaeological sites in the world. Selected mountains were used as places of pilgrimage in the context of sacrifices and offerings performed five centuries ago during state-sponsored ceremonies called capacochas. Diverse attributes could have been involved in the selection of the mountains to be crowned with imperial summit shrines. Archaeological examples are from Andean mountains above 5,000 meters in elevation, where I have been conducting high-altitude explorations on more than one hundred peaks since 1996. The evidence from archaeological surveys is contrasted with ethnographic data and references from ethno-historical sources. Attributes such as the altitude of the mountains and their visibility, as well as the accessibility of the summits, are taken into consideration in the analysis, pondering the strategies used by the Incas to cope with glaciers climbs, active volcanoes and snowcapped peaks.

Lung ultrasound examination is becoming an even more important part of pulmonologists’ clinical routine. As indicated in the literature, the coordinates of any findings on lung parenchyma are based on surface landmarks or conventional quadrants. In our experience we have noticed that lung fissures are clearly detectable as interruptions of the pleural line, but this has never been investigated previously. The aim of this study was to evaluate whether lung fissures are detectable under normal conditions in routine clinical practice.