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Background: The management of chronic obstructive pulmonary disease (COPD) lacks standardization due to the diverse clinical presentation, comorbidities, and limited acceptance of recommended approaches by physicians. To address this, a multicenter study was conducted among Italian respiratory physicians to assess consensus on COPD management and pharmacological treatment., Methods: The study employed the Delphi process using the Estimate-Talk-Estimate method, involving a scientific board and expert panel. During a 6-month period, the scientific board conducted the first Delphi round and identified 11 broad areas of COPD management to be evaluated while the second Delphi round translated all 11 items into statements. The statements were subsequently presented to the expert panel for independent rating on a nine-point scale. Consensus was considered achieved if the median score was 7 or higher. Consistently high levels of consensus were observed in the first rating, allowing the scientific board to finalize the statements without requiring further rounds., Results: Topics generating substantial discussion included the pre-COPD phase, patient-reported outcomes, direct escalation from a single bronchodilator to triple therapy, and the role of adverse events, particularly pneumonia, in guiding triple therapy prescriptions. Notably, these topics exhibited higher standard deviations, indicating greater variation in expert opinions., Conclusions: The study emphasized the significance that Italian pulmonologists attribute to managing mortality, tailoring treatments, and addressing cardiovascular comorbidities in COPD patients. While unanimous consensus was not achieved for all statements, the results provide valuable insights to inform clinical decision-making among physicians and contribute to a better understanding of COPD management practices in Italy.

Hidradenitis suppurativa (HS) is a frequent chronic inflammatory skin condition primarily affecting areas rich in apocrine sweat glands, presenting with comedones, papules, nodules, and abscesses, as well as tunnels and hypertrophic scarring. Despite its prevalence and impact on quality of life, the pathogenesis of HS remains incompletely understood. Notably, its diagnosis often suffers from delays and misidentification, therefore an improved education for healthcare providers is mandatory. Moreover, HS is frequently associated with systemic comorbidities and a multidisciplinary approach is suggested for its management. Recognizing these challenges, a group of Italian HS experts and patients convened to develop consensus guidelines via the Nominal Group Technique. Through iterative meetings and remote collaboration, they identified key areas for improvement and formulated consensus statements to guide healthcare providers in delivering optimal care. This collaborative effort highlights the importance of standardized approaches and interdisciplinary collaboration in managing HS effectively., (© 2024. The Author(s).)

More than half of the world's rivers dry up periodically, but our understanding of the biological communities in dry riverbeds remains limited. Specifically, the roles of dispersal, environmental filtering and biotic interactions in driving biodiversity in dry rivers are poorly understood. Here, we conduct a large-scale coordinated survey of patterns and drivers of biodiversity in dry riverbeds. We focus on eight major taxa, including microorganisms, invertebrates and plants: Algae, Archaea, Bacteria, Fungi, Protozoa, Arthropods, Nematodes and Streptophyta. We use environmental DNA metabarcoding to assess biodiversity in dry sediments collected over a 1-year period from 84 non-perennial rivers across 19 countries on four continents. Both direct factors, such as nutrient and carbon availability, and indirect factors such as climate influence the local biodiversity of most taxa. Limited resource availability and prolonged dry phases favor oligotrophic microbial taxa. Co-variation among taxa, particularly Bacteria, Fungi, Algae and Protozoa, explain more spatial variation in community composition than dispersal or environmental gradients. This finding suggests that biotic interactions or unmeasured ecological and evolutionary factors may strongly influence communities during dry phases, altering biodiversity responses to global changes., (© 2024. The Author(s).)

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified 10 areas of interest based on published evidence and personal experience: (1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); (2) tailoring surgery to HS characteristics; (3) wide local excision; (4) presurgery biologic treatment; (5) concomitant biologic and surgical treatments; (6) pre- and postsurgery management; (7) antibiotic systemic therapy; (8) biologic therapy after radical surgery; (9) management of adverse events to biologics; and (10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Myasthenia gravis (MG) is a rare, autoimmune, neurological disorder. Most MG patients have autoantibodies against acetylcholine receptors (AChRs). Some have autoantibodies against muscle-specific tyrosine kinase (MuSK) or lipoprotein-receptor-related protein 4 (LRP4), and some are seronegative. Standard of care, which includes anti-cholinesterase drugs, thymectomy, corticosteroids (CS), and off-label use of non-steroidal immunosuppressive drugs (NSISTs), is bounded by potential side effects and limited efficacy in refractory generalized MG (gMG) patients. This highlights the need for new therapeutic approaches for MG. Eculizumab, a monoclonal antibody that inhibits the complement system, has been recently approved in Italy for refractory gMG. A panel of 11 experts met to discuss unmet therapeutic needs in the acute and chronic phases of the disease, as well as the standard of care for refractory patients. Survival was emphasized as an acute phase outcome. In the chronic phase, persistent remission and early recognition of exacerbations to prevent myasthenic crisis and respiratory failure were considered crucial. Refractory patients require treatments with fast onset of action, improved tolerability, and the ability to slow disease progression and increase life expectancy. The Panel agreed that eculizumab would presumably meet the therapeutic needs of many refractory gMG patients. The panel concluded that the unmet needs of current standard of care treatments for gMG are significant. Evaluating new therapeutic options accurately is essential to find the best balance between efficacy and tolerability for each patient. Collecting real-world data on novel molecules in routine clinical practice is necessary to address unmet needs., (© 2024. Fondazione Società Italiana di Neurologia.)

We performed a comprehensive systematic targeted literature review and used the Delphi method to formulate expert consensus statements to guide the treatment of adult-onset Still's disease (AOSD) to achieve an early and long-term remission. Seven candidate statements were generated and reached consensus in the first round of voting by the panel of experts. We postulate: (i) In patients with AOSD with predominant arthritis at onset who achieved no disease control with glucocorticoids (GCs), the use of methotrexate can be considered, whereas the use of cyclosporin A and low-dose GCs should not (Statements 1-3); (ii) In patients with AOSD with poor prognostic factors at diagnosis, an IL-1 inhibitor (IL-1i) in addition to GCs should be taken into consideration as early as possible (Statement 4); (iii) A switch to an IL-6 inhibitor (IL-6i) may be considered in patients with AOSD with prevalent joint involvement, who are unresponsive or intolerant to IL-1i (Statement 5); (iv) Drug tapering or discontinuation may be considered in patients who achieved a sustained clinical and laboratory remission with IL-1i (Statement 6); (v) In patients with AOSD who failed to attain a good clinical response with an IL-1i, switching to an IL-6i may be considered in alternative to a different IL-1i. TNF-inhibitors may be considered as a further choice in patients with a prominent joint involvement (Statement 7). These statements will help clinicians in treatment decision making in patients with AOSD., Competing Interests: Declaration of Competing Interest RP received fees from Novartis; RC received speaker's and paid consultation fees from Abbvie, BMS, Lilly. Pfizer, Galapagos, Novartis, MSD. Janssen, Fresenius-Kabi, Sandoz, UCB. The remaining authors have nothing to declare., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Advanced urothelial carcinoma remains aggressive and very hard to cure, while new treatments will pose a challenge for clinicians and healthcare funding policymakers alike. The U-CHANGE Project aimed to redesign the current model of care for advanced urothelial carcinoma patients to identify limitations ("as is" scenario) and recommend future actions ("to be" scenario)., Methods: Twenty-three subject-matter experts, divided into three groups, analyzed the two scenarios as part of a multidimensional consensus process, developing statements for specific domains of the disease, and a simplified Delphi methodology was used to establish consensus among the experts., Results: Recommended actions included increasing awareness of the disease, increased training of healthcare professionals, improvement of screening strategies and care pathways, increased support for patients and caregivers and relevant recommendations from molecular tumor boards when comprehensive genomic profiling has to be provided for appropriate patient selection to ad hoc targeted therapies., Discussion: While the innovative new targeted agents have the potential to significantly alter the clinical approach to this highly aggressive disease, the U-CHANGE Project experience shows that the use of these new agents will require a radical shift in the entire model of care, implementing sustainable changes which anticipate the benefits of future treatments, capable of targeting the right patient with the right agent at different stages of the disease., Competing Interests: GLC has received speaker fees, research and educational grants from Abbott, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi and Pfizer. GNC has received speaker fees, research and educational grants from Janssen, Astellas, Bayer, Recordati, MSD, Astrazeneca, IPSEN. VB has received speakers fees from Janssen and Astellas. PB has received speaker fees, research and educational grants from Astellas, Astrazeneca, BeiGene, Dephaforum, EISAI, Eli Lilly, Excerptamedica, Gilead, Janssen-Cilag SpA, Merck Serono Spa, MSD, Novartis, PierreFabre, Pharmagenesis, Reithera srl, Roche, Rottapharm, Sanofi, Servier, Takeda, Takis, and Toscana Life Science. Outside of the submitted work, PZ reports personal fees for advisory roles, speaker engagements and travel and accommodation expenses from MSD, Merck Serono Spa, Astellas, Janssen-Cilag SpA, Sanofi, Ipsen, Pizer, Noartis, BMS, Amgen, AstraZeneca, Roche and Bayer. SB was advisory board or Steering Committee Member uncompensated for: Bayer, Astellas, Janssen, Pfizer, BMS, Roche, Ipsen, MSD, AAA, Sanofi, Merck, Astrazeneca. GP reports fees as advisory board and expertise dossier on clinical-epidemiological evaluations for Astellas, BMS, Merck, MSD. RI served as an advisory board member or consultant for Astellas, Pfizer, Janssen, Sanofi, IPSEN, MSD, BMS, Novartis, EISAI; received institutional support for research project from Pfizer and BMS. AG has received speakers fees from Amgen. MB received research grants and speaker fees from MSD, Leica and speaker fees from Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer SL declared a shared affiliation with the author EOS to the handling editor at the time of review., (Copyright © 2023 Bracarda, Iacovelli, Baldazzi, Zucali, Gernone, Conti, Pappagallo, Brunelli, Bruzzi, Fiorini, Magenta, Diomede, Mereta, D’Aria, Magliano, Liberatori, Cantù, Croce, Eandi, Colombo, Ferrante, Salè, Marinozzi, Lenzi, Remiddi and Remiddi.)

The recent approval of PARP inhibitors for the treatment of metastatic -castration-resistant prostate cancer (mCRPC) patients with BRCA mutations firstly introduced the possibility of proposing a targeted treatment in this disease. However, the availability of this therapeutic option raises a number of questions concerning the management of prostate cancer in everyday clinical practice: the timing and method of detecting BRCA mutations, the therapeutic implications of the detection, and the screening of the members of the family of a prostate cancer patient with a BRCA alteration. These challenging issues led the Italian Society for Uro-Oncology (SIUrO) to organise a Consensus Conference aimed to develop suggestions capable of supporting clinicians managing prostate cancer patients. The present paper described the development of the statements discussed during the consensus, which involved all of the most important Italian scientific societies engaged in the multi-disciplinary and multi-professional management of the disease., Competing Interests: Declaration of Competing Interest Alberto Lapini has received fees or honoraria for acting as an advisor to Medac, Bayer, MSD and Janssen, Orazio Caffo has received fees or honoraria for acting as speaker or as an advisor to AAA, Astellas, Astra Zeneca, Bayer, Ipsen, Janssen, MSD, Pfizer, Giario Natale Conti has received fees or honoraria for acting as an advisor to Janssen, Astellas, Bayer, Recordati, MSD, Astrazeneca and Ipsen, Giovanni Luigi Pappagallo has received fees or honoraria for acting as an advisor to AAA, Astellas, Astrazeneca, Janssen, Marzia Del Re has received fees from Astellas, AstraZeneca, Celgene, Novartis, Pfizer, BioRad, Janssen, Sanofi-Aventis, Roche, MSD, Lilly and Ipsen; and honoraria for acting as an advisor to Astra Zeneca, MSD, Ipsen, Janssen, Sanofi-Aventis, and Amgen, Francesca Castiglione has received fees from AstraZeneca, Novartis, Roche, MSD, GSK, and honoraria for acting as an advisor to Astra Zeneca, MSD, and Amgen, Matteo Brunelli has received fees from MSD, Janssen, Genactis, NTP, Oncotech, Roberto Iacovelli has received fees or honoraria for acting as an advisor to Astellas, BMS, EISAI, IPSEN, Janssen, MSD, Novartis, Pfizer, Sanofi. Consultant for Astellas, EISAI, MSD, Pfizer, Ugo De Giorgi received honoraria for advisory boards or speaker fees for Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Roche, Novartis, Clovis, GSK, AstraZeneca, institutional research grants from AstraZeneca, Sanofi and Roche, Sergio Bracarda has received fees or honoraria for acting as an advisor from or steering committee member from AAA, Astellas, AstraZeneca, Bayer, BMS, Janssen, Ipsen, Merck, MSD, Pfizer, Roche, Sanofi. The other authors did not have conflicts of interest to be declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Non-metastatic castration resistant prostate cancer (nmCRPC) is a clinical setting defined as confirmed rising levels of PSA in patients treated with ADT but without detectable metastases on conventional imaging with computerized tomography (CT) and technetium-99 m scintigraphy. Men with nmCRPC and a PSA doubling time (PSADT) ≤ 10 months are considered at high risk of rapidly developing metastases with a consequent possible impact on survival. Three recent phase III trials have demonstrated, in this setting, the efficacy of adding a next-generation androgen receptor targeted agent (ARTA) to ADT in respect to ADT only, in delaying the development of metastases (metastasis-free survival, MFS) and prolong overall survival. The magnitude of clinical benefit of these agents was even more meaningful if considering the low incidence of drug related adverse events. Our review described the latest advances in the management of nmCRPC, deriving from the pivotal clinical trials, SPARTAN, PROSPER and ARAMIS, in order to support clinicians to optimally manage these patients. Of note, the emergence of novel, more accurate, next-generation imaging techniques (including Ga PSMA-PET/CT), as well as eventual future tumor biomarkers, is modifying the entity and definition of the nmCRPC setting, with a consequent impact on patient's diagnosis and management., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Alfredo Berruti received fees as a speaker by AMGEN, AAA-Novartis, Janssen, Ipsen, for advisory role: IPSEN, Janssen, Astellas, AMGEN, AAA-Novartis. Sergio Bracarda acted (uncompensated) as an Advisory Board or Steering Committee Member for: Pfizer, Astellas, Janssen, Bayer, BMS, Ipsen, Merck, MSD/Eisai, AAA-Novartis, AstraZeneca, Sanofi-Genzyme, Roche. Orazio Caffo received fees as a speaker by Astellas, Janssen, MSD, Astra Zeneca, Ipsen; as an advisor by AAA, Aatellas, Bayer, Janssen, MSD. Enrico Cortesi received fees from Novartis, Astellas, Bayer, Roche, BMS, MSD, EISAI, Ipsen, SIRTEX, research grant from Merck, fellowships grant from Novartis, Amgen. Rolando D’Angelillo nothing to declare. Marzia Del Re received fees from Astellas, AstraZeneca, Celgene, Novartis, Pfizer, Bio-Rad, Janssen, Sanofi-Aventis, Roche, MSD, Lilly and Ipsen; honoraria for advisory role: Astra Zeneca, MSD, Ipsen, Janssen, Sanofi-Aventis, Amgen. Gaetano Facchini received fees as a speaker by Janssen, Astellas, Amgen; honoraria for advisory role: Astra Zeneca, Bayer. Giovanni Pappagallo honoraria for advisory role: AAA, Alnylam, Astrazeneca, Astellas, Bayer, BMS, Celgene, Daiichi-Sankyo, GSK, Ipsen, Janssen, Merck, MSD, Pierre Fabre, Pfizer, Roche, Vertex. Giuseppe Procopio honoraria for advisory role: Astrazeneca, Bayer, BMS, Eisai, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Sanofy. Research grant Astellas, Ipsen, Novartis. Roberto Sabbatini received fees from Astellas, Pfizer, Janssen, MSD, Bayer, Amgen and Ipsen; honoraria for advisory role: MSD, Ipsen, Janssen, Pfizer, BMS, Merk. Daniele Santini honoraria for advisory role: Amgen, Astrazeneca, Bayer, BMS, Eisai, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer. Research grant: BMS, Eisai, Astellas, Ipsen, Novartis]., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A group of Italian experts in impetigo medical care sought to define 10 statements to describe the ideal characteristics of the best local antibiotic treatments, and to provide relevant information re- garding their appropriate use and prescription that should be considered in clinical practice for impetigo management., Objective: A group of Italian experts in impetigo medical care sought to define 10 statements to describe the ideal characteristics of the best local antibiotic treatments, and to provide relevant information regarding their appropriate use and prescription that should be considered in clinical practice for impetigo management., Methods: A consensus on ideal features of antibiotic therapy for the treatment of impetigo was appraised by an online Delphi-based method, based on a panel of 61 infectious disease specialists, pediatricians, and dermatologists coordinated by a scientific committee of 5 experts specializing in impetigo management., Results: Full or very high consensus was reached on the 10 statements identified to describe the characteristics of the best hypothetic antibiotic therapy for impetigo together with indications for appropriate antibiotics use., Conclusions: Several criteria have to be considered when selecting topical antibacterial therapy for impetigo. Beyond efficacy and safety, antimicrobial susceptibility and pharmacological characteristics of the agent are essential points. Formulation of the antimicrobial product is fundamental, as well as patient and caregiver preference, to facilitate therapeutic adherence, to achieve the infection control, and to obtain the best benefit from treatment ( Curr Ther Res Clin Exp. 2023; 84:XXXXXX)., (© 2022 Published by Elsevier Inc.)

Obesity negatively affects physical and psychological health and increases health care costs. Although there is increasing interest in early diagnosis and timely intervention, there are several principles of care included in the current guidelines for clinical management of obesity that can potentially be updated and improved to address the "clinical inertia" and, consequently, to optimize the management of adult obesity. Using an online Delphi-based process, an Italian board of experts involved in the management of obesity discussed the usefulness of a pro-active approach to the care of patients with obesity, providing a consensus document with practical indications to identify risk factors for morbidity and death and raise awareness throughout the treatment continuum, including the early stages of the disease. In clinical practice, it seems inappropriate to delay an intervention that could avoid progression to a more severe level of obesity and/or prevent the onset of obesity-related comorbidities.Level of evidence Level V, report of expert committee., (© 2022. The Author(s).)

Metastatic hormone-sensitive prostate cancer (mHSPC) is usually categorized as high- or low-volume disease. This is relevant because low- and high-volume metastatic disease are associated with different outcomes, and thus management of the two forms should differ. Although some definitions have been reported, the concept of oligometastatic disease is not so clearly defined, giving rise to further variability in the choice of treatment, mainly between systemic agents and radiotherapy, especially in the era of metastasis-directed therapy. With the aim of providing clinicians with guidance on best practice, a group of medical and radiation oncologists, experts in prostate cancer, used the round robin method to generate a series of consensus statements on management of low-volume mHSPC. Consensus was obtained on three major areas of controversy: (1) with regard to clinical definitions of mHSPC, it was held that oligometastatic and low-volume disease refer to different concepts and should not be used interchangeably; (2) regarding therapy of de novo low-volume metastatic disease, androgen deprivation therapy alone can be considered undertreatment, and all patients should be evaluated for systemic treatment combinations; local therapy should not be denied in patients with mHSPC, regardless of the intensity of systemic therapy, and metastasis-directed therapy can be proposed in selected cases; (3) with regard to treatment of metachronous metastatic disease, patients should be evaluated for systemic treatment combinations. Metastasis-directed therapy can be proposed to delay systemic treatment in selected cases, especially if prostate-specific membrane antigen positron emission tomography staging has been performed and when indolent disease occurs. It is hoped that clinicians treating patients with mHSPC in daily practice will find this expert opinion of value.

Background: The goal of mucoactive therapies in cystic fibrosis (CF) is to enhance sputum clearance and to reduce a progressive decline in lung function over the patient's lifetime. We aimed to investigate the level of consensus among specialists from Italian CF Centers on appropriateness of therapeutic use of dornase alfa (rhDNase) for CF patients., Method: A consensus on appropriate prescribing in CF mucoactive agents was appraised by an online Delphi method, based on a panel of 27 pulmonologists, coordinated by a Scientific Committee of six experts in medical care of patients with CF., Results: Full or very high consensus was reached on several issues related to therapeutic use of dornase alfa for CF patients in clinical practice., Conclusions: The consensus reached on a number of topics regarding use of mucoactive agents in patients with CF can help guide clinicians in daily practice based on expert experience and define the most appropriate therapeutic strategy for the individual patient., Competing Interests: Dr. Blasi reports grants and personal fees from AstraZeneca, grants from Bayer, grants and personal fees from Chiesi, grants and personal fees from GSK, personal fees from Grifols, personal fees from Guidotti, personal fees from INSMED, grants and personal fees from Menarini, personal fees from Mylan, personal fees from Novartis, grants and personal fees from Pfizer, personal fees from Zambon, personal fees from Vertex, in the last 3 years outside the submitted work. Dr Volpi reports personal fees as a consultant for: Chiesi, Mylan, and Vertex in the last 3 years outside the submitted work. Giovanni Pappagallo, Vincenzo Carnovale, Carla Colombo, Valeria Raia, declare that they have no conflicts of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Many treatment approaches are now available for neuroendocrine neoplasms (NENs). While several societies have issued guidelines for diagnosis and treatment of NENs, there are still areas of controversy for which there is limited guidance. Expert opinion can thus be of support where firm recommendations are lacking. A group of experts met to formulate 14 statements relative to diagnosis and treatment of NENs and presented herein. The nominal group and estimate-talk-estimate techniques were used. The statements covered a broad range of topics from tools for diagnosis to follow-up, evaluation of response, treatment efficacy, therapeutic sequence, and watchful waiting. Initial prognostic characterization should be based on clinical information as well as histopathological analysis and morphological and functional imaging. It is also crucial to optimize RLT for patients with a NEN starting from accurate characterization of the patient and disease. Follow-up should be patient/tumor tailored with a shared plan about timing and type of imaging procedures to use to avoid safety issues. It is also stressed that patient-reported outcomes should receive greater attention, and that a multidisciplinary approach should be mandatory. Due to the clinical heterogeneity and relative lack of definitive evidence for NENs, personalization of diagnostic-therapeutic work-up is crucial.

We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3-G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion ( p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes ( p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods ( p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.

In the past decade, nine antibody-drug conjugates (ADCs) have been approved for the treatment of various tumors, four of which specifically for solid malignancies. ADCs deliver the cytotoxic payload to the cancer site, thereby improving chemotherapy efficacy while reducing systemic drug exposure and toxicity. With their high selectivity, ADCs are associated with a manageable side-effect profile, with nausea and vomiting being among the most frequent toxicities, although this may vary according to the respective ADC and the associated payload. Information about the emetic risk of the new ADC compounds is limited. Three virtual focus groups of Italian oncologists were held to raise awareness on the importance of an antiemetic prophylaxis regimen to prevent and mitigate ADC-associated emesis and its sequelae. After reviewing published evidence and guidelines, the three expert panels shared their experience on the early use of ADCs gained through the participation in specific clinical trials and their clinical practice. The following issues were discussed: antiemetic therapy during trastuzumab deruxtecan treatment, with a protocol adopted at the San Raffaele Hospital (Milan, Italy); the use of steroids; the management of anticipatory nausea during trastuzumab deruxtecan therapy; nutritional counselling; and effective doctor-patient communication. The experts acknowledged that recommendations should be drug-specific, and formulated opinion-based advice intended to guide physicians in their daily practice until further evidence emerges.

Background: Regular treatment to prevent bleeding and consequent joint deterioration (prophylaxis) is the standard of care for persons with severe hemophilia A, traditionally based on intravenous infusions of the deficient clotting FVIII concentrates (CFCs). In recent years, extended half-life (EHL) CFCs and the non-replacement agent emicizumab, subcutaneously administered, have reduced the treatment burden., Methods: To compare and integrate the opinions on the different therapies available, eight hemophilia specialists were involved in drafting items of interest and relative statements through the Estimate-Talk-Estimate (ETE) method ("mini-Delphi"), in this way reaching consensus., Results: Eighteen items were identified, then harmonized to 10, and a statement was generated for each. These statements highlight the importance of personalized prophylaxis regimens. CFCs, particularly EHL products, seem more suitable for this, despite the challenging intravenous (i.v.) administration. Limited real-world experience, particularly in some clinical settings, and the lack of evidence on long-term safety and efficacy of non-replacement agents, require careful individual risk/benefit assessment and multidisciplinary data collection., Conclusions: The increased treatment options extend the opportunities of personalized prophylaxis, the mainstay of modern management of hemophilia. Close, long-term clinical and laboratory follow-up of patients using newer therapeutic approaches by specialized hemophilia treatment centers is needed.

Aims: According to The Cancer Genome Atlas (TCGA), around 9% of bladder carcinomas usually show abnormalities of the murine double minute 2 (MDM2) gene, but a few studies have been investigated them. We profiled MDM2 gene amplification in a series of urothelial carcinomas (UC) considering the molecular subtypes and expression of programmed death ligand 1 (PD-L1)., Methods: 117 patients with muscle-invasive UC (pT2-3) without (N0) or with (N+) lymph-node metastases were revised. Only cases with availability of in toto specimens and follow-up were studied. Tissue microarray was built. p53, ER, RB1, GATA-3, CK20, CK5/6, CD44 and PD-L1 (clone sp263) immunoexpression was evaluated. Fluorescent in situ hybridisation was assessed by using the HER-2/neu, FGFR-3, CDKN2A and MDM2 probes. True (ratio 12q/CEP12 >2) MDM2 gene amplification was distinguished from polyploidy/gains (ratio <2, absolute copy number of MDM-2 >2). MDM2 and PD-L1 values were correlated to the TCGA molecular phenotypes. Statistical analysis was performed., Results: 6/50 (12%) cases (5 N0 and 1 N+) were amplified for MDM2 without matching to molecular phenotypes. Of 50, 14 (37%) cases expressed PD-L1 at 1% cut-off; 3/50 (9%) at >50% cut-off; of these, 2 cases on side of neoplasia among inflammatory cells. Only one out of six (17%) cases amplified for MDM2 showed expression (>50% cut-off) of PD-L1. MDM2 amplification was independent to all documented profiles (k test=0.3) and was prevalent in recurrent UC., Conclusion: MDM2 amplification has been seen in both PD-L1 positive and negative muscle-invasive bladder UC independently from the TCGA molecular phenotypes. MDM2 and PD-L1 might be assessed in order to predict a better response to combo/single targeted therapies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Treatment for locally advanced differentiated thyroid cancer is surgery followed by radioiodine while the role of adjuvant external beam radiotherapy (EBRT) is debated., Methods: The panel of the Italian Association of Radiotherapy and Clinical Oncology developed a clinical recommendation on the addition of EBRT to radioiodine after surgery for locally advanced differentiated thyroid cancer by using the Grades of Recommendation, Assessment, Development, and Evaluation methodology and the Evidence to Decision framework. A systematic review with meta-analysis about this topic was conducted with a focus on outcome of benefits and toxicity., Results: Locoregional control was improved by EBRT while no considerable toxicity impact was reported., Conclusion: The panel judged uncertain the benefit/harms balance; final recommendation was conditional both for EBRT + radioiodine and radioiodine alone in the adjuvant setting.

Background: Pre-clinical data suggest that docetaxel and enzalutamide interfere with androgen receptor translocation and signalling. The aim of this study is to assess the efficacy of their concurrent administration in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC)., Methods: In this open-label, randomised, phase II trial, previously untreated mCRPC patients were randomised 1:1 to receive eight 21-d courses of docetaxel 75 mg/m 2 , oral prednisone 5 mg twice daily and oral enzalutamide 160 mg/d (arm DE), or the same treatment without enzalutamide (arm D). The primary end-point was the percentage of patients without investigator-assessed disease progression 6 months after the first docetaxel administration., Results: The 246 eligible patients were randomly assigned to receive docetaxel, prednisone and enzalutamide (n = 120) or docetaxel and prednisone (n = 126). The 6-month progression rate was 12.5% (95% confidence interval [CI] 8.1-20.6) in arm DE and 27.8% (95% CI 22.8-39.4) in arm D (chi-squared test 10.01; P = 0.002). The most frequent grade III-IV adverse events were fatigue (12.5% in arm DE versus 5.6% in arm D), febrile neutropenia (9.3% versus 4.0%) and neutropenia (7.6% versus 5.6%)., Conclusions: The combination of enzalutamide and docetaxel appears to be more clinically beneficial than docetaxel alone in previously untreated mCRPC patients, although serious adverse events were more frequent. Our findings suggest that first-line treatment with this combination could lead to an additional clinical benefit when prompt and prolonged disease control is simultaneously required. Clearly, these results should be considered cautiously because of the study's phase II design and the absence of an overall survival benefit., Trial Registration Numbers: EudraCT 2014-000175-43 - NCT02453009., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Orazio Caffo is an advisor to Janssen, MSD and Bayer, and a speaker for Astellas, AstraZeneca, Bayer, Janssen, MSD, Pfizer and Sanofi. Cinzia Ortega is an advisor to Janssen, Astellas, Pfizer, Novartis and MSD, and a speaker for MSD, BMS and Sanofi. Donatello Gasparro is a speaker for and an advisor to Sanofi and Astellas. Vittorina Zagonel is an advisor to Bristol-Myers Squibb, MSD, Eisai and Italfarmaco, and a speaker for Roche, Bristol-Myers Squibb, Astellas Pharma, Servier, AstraZeneca, MSD, Janssen and Ipsen. Roberto Iacovelli is an advisor to Pfizer, Ipsen, Janssen, Astellas, MSD and BMS. Ugo De Giorgi is a consultant of Astellas Pharma, Bayer, BMS, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche and Sanofi. Elena Verri is an advisor to Astellas, Bayer, Janssen and Sanofi. Sebastiano Buti is a speaker for and advisor to BMS, Pfizer, Pierre-Fabre, MSD, Ipsen, Roche, Eli-Lilly, AstraZeneca and Novartis. Marco Maruzzo is an advisor to Pfizer, BMS, Janssen, MSD, Merck Serono and Ipsen. Giovanni Pappagallo is a counsellor and trainer for Astellas, AstraZeneca, Daiichi-Sankyo, Ipsen, Janssen, MSD, Pierre Fabre, Pfizer, Roche, Servier and Teva. Massimo Aglietta is an advisor to Bayer, BMS, Merck and Novartis, and has received travel support from BMS, Merck and Tesaro. Maurizio Nicodemo is a speaker for and an advisor to Bristol-Myers Squibb, Ipsen, Molteni and Janssen. Roberto Sabbatini is an advisor to Janssen, and a speaker for Astellas, Janssen and Sanofi. Franco Morelli is a speaker for MSD and Pfizer. Francesco Carrozza is a speaker for Janssen. Camillo Porta is a consultant of and speaker for Angelini, AstraZeneca, Bristol-Myers Squibb, Eisai, EUSA, General Electric, Ipsen, Merck, MSD, Novartis and Pfizer; an expert witness for EUSA and Pfizer; a member of the Protocol Steering Committee of Bristol-Myers Squibb, Eisai and EUSA and has received travel support from Roche. The remaining authors have no conflict of interest to be declared, (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Currently, conventional treatments for metastatic RCC (mRCC) include immune-based combination regimens and/or targeted therapies, the latter mainly acting on angiogenesis, a key element of the process of tumor growth and spread. Although these agents proved able to improve patients' outcomes, drug resistance and disease progression are still experienced by a substantial number of VEGFR-TKIs-treated mRCC patients. Following the inhibition of the VEGF/VEGFRs axis, two strategies have emerged: either specifically targeting resistance pathways, at the same time continuing to inhibit angiogenesis, or using a completely different approach aimed at re-activating the immune system through the use of inhibitors of specific negative immune checkpoints. These two approaches, practically represented by the use of either cabozantinib or nivolumab, seem to remain a rational therapeutic approach also when first-line immune-based combinations are used. The objective of this study is to design a preferential therapeutic pathway for the second-line treatment of mRCC. The procedure applied in this project was a group discussion, based on the Nominal Group Technique (NGT) method in a meeting session, aimed at defining the therapeutic choice for the second-line treatment of mRCC. The NGT process defined the most relevant parameters that, according to the interviewed panelists, clinicians should consider for the selection of the second-line therapy in the context of advanced renal cell carcinoma of mRCC. The algorithm developed for the treatment selection as a result of this process should thus be considered by clinicians as reference for therapy selection., Plain Language Summary: The result of this paper was the definition of an algorithm intended to suggest a preferential therapeutic pathway considering both the outputs of the Nominal Group Technique (NGT) process and the actual clinical practice and the experience of selected panelists. During the NGT process and the discussion phase, panelists defined the most important parameters to be included in the algorithm that are important for the treatment definition. Cabozantinib and nivolumab are identified as the most reasonable therapeutic options for patients progressing after first-line treatment and are the medication options included in the algorithm for therapy selection., Competing Interests: Conflict of interest statement: - Valentina Guadalupi in the last two years has had financial or working relationships with Janssen - Giacomo Cartenì works as responsible for research and development at Kerubin Digital Therapeutic - Roberto Iacovelli acted as a Consultant and/or a Speaker for Pfizer, Ipsen, MSD, Sanofi, Janssen - Camillo Porta acted as a Consultant and/or a Speaker for Ipsen, BMS, MSD, Astra Zeneca, Pfizer, Eisai, EUSA and General Electrics; he acted also as an Expert Testimony for both Pfizer and EUSA and is a protocol steering committee member for BMS, EUSA and Eisai - Giovanni Pappagallo acted as a Consultant and/or Speaker (training or advisory board or clinical epidemiological evaluations) for Astellas, AstraZeneca, Clovis, Ipsen, Janssen, MSD. Pierre Fabre, Pfizer, Roche, Sanofi, Servier, Teva - Riccardo Ricotta acted as a Consultant and/or a Speaker for BMS, Ipsen, Janssen, MSD, Pfizer, Sanofi-Genzyme - Giuseppe Procopio acted as a Consultant and/or a Speaker for Bayer, BMS, Novartis, Amgen, Pfizer, Janssen, Ipsen, Boehringer, (© The Author(s), 2021.)

Two bench-scale Self-Forming Dynamic Membrane BioReactors (SFD MBR), equipped with 50 μm nylon meshes were set up and operated under aerobic conditions in order to treat canning and winery wastewaters. The results showed different behaviors of the two systems, confirming the strong dependence of SFD MBR performance on the type of biomass and, in turn, on the type of stream being treated. Both plants achieved good results in terms of effluent quality, demonstrating the suitability of the proposed technology. Median values of effluent turbidity were 2.7 and 15.4 NTU (Nephelometric Turbidity Units) in the reactors fed with canning wastewater and winery wastewater, respectively. The removal of organic matter (as COD, Chemical Oxygen Demand) was consistently above 90 %, although the retention of suspended solids was variable and somewhat dependent on operating conditions and feed composition. The activated sludge characteristics were observed to affect filtration performance and in particular the capillary suction time (CST) was a possible indicator of efficiency, with a threshold value of 11 s above which filtration performance decreased. This parameter is proposed as an early warning tool for changes in the filtration performance of an SFD MBR, both for effluent quality and cleaning requirements., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Adding pertuzumab to standard trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival (IDFS) in the APHINITY trial. However, the magnitude of benefit was marginal in the overall population. Methods: We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) analysis on data from APHINITY to build summary-of-findings tables to evaluate the efficacy, safety and quality of evidence of predefined clinical outcomes for the addition of pertuzumab to trastuzumab-based adjuvant therapy in patients with high-risk HER2-positive early breast cancer. Results: Pertuzumab significantly improved 3-year, event-free, absolute benefit in disease-free survival, IDFS and distant relapse-free interval (DFRI) in patients with node-positive or hormone receptor-negative disease. The analysis provides strength of evidence supporting the addition of pertuzumab in this patient population.

Introduction: The sequential use of a number of new agents (NAs) have improved the overall survival (OS) of patients with metastatic castration-resistant prostate cancer whose disease progresses after docetaxel (DOC) treatment. The aim of this study was to assess the cumulative survival outcomes of different sequencing strategies by evaluating the individual data from published studies of patients treated with a post-DOC treatment sequence of 2 NAs., Patients and Methods: The patients' individual data were analyzed to investigate whether different sequencing strategies lead to differences in OS., Results: We analyzed the data of 1099 evaluable patients. Among the patients treated with a second-line new hormone agent (NHA), median OS from the start of third-line treatment was significantly longer in the patients treated with cabazitaxel (CABA) than in those treated with abiraterone acetate or enzalutamide. Median cumulative OS (cumOS) from the start of second-line treatment was 21.1 months in the patients who received NHA then NHA, 22.1 months in those who received NHA then CABA, and 21.0 months in those who received CABA then NHA. Among the patients with a second-line progression-free survival of ≥6 months, median cumOS was significantly longer in patients who received CABA-including sequences than in those treated with NHA then NHA sequences (29.5 vs. 24.8 months; P = .03)., Conclusion: Our findings suggest that the sequential use of NAs with different mechanisms of action improves cumOS regardless of the order in which they are administered, thus supporting the hypothesis of cross-resistance between the 2 NHAs., (Copyright © 2019. Published by Elsevier Inc.)

Background: The availability of a number of agents that are efficacious in patients with metastatic prostate cancer (mPC) has led to them being used sequentially, and this has prolonged patient survival. However, in order to maximize their efficacy, clinicians need to be able to obtain a reliable picture of disease evolution by means of monitoring procedures., Methods: As the intensive monitoring protocols used in pivotal trials cannot be adopted in everyday clinical practice and there is no agreement among the available guidelines, a multidisciplinary panel of Italian experts met to develop recommendations for monitoring mPC patients using a modified Delphi method., Results: The consensus project considered methods of clinically, radiographically, and biochemically monitoring patients with metastatic hormone-sensitive and metastatic castration-resistant prostate cancer undergoing chemotherapy and/or hormonal treatment. The panelists also considered the methods and timing of monitoring castration levels, bone health, and the metabolic syndrome during androgen deprivation therapy., Conclusions: The recommendations, which were drawn up by experts following a formal and validated consensus procedure, will help clinicians face the everyday challenges of monitoring metastatic prostate cancer patients., Competing Interests: Alberto Lapini: None Orazio Caffo: Advisor and/or speaker for Janssen, Sanofi, Astellas, Bayer, Astra Zeneca, Pfizer Giovanni Luigi Pappagallo: none Roberto Iacovelli: Advisor for Astellas, Janssen, Ipsen, Pfizer, Novartis, MSD, BMS—Speaker for MSD, Ipsen, Sanofi Rolando Maria D’Angelillo: None Vittorio Vavassori: None Roberta Ceccarelli: None Sergio Bracarda: Advisor for Pfizer, BMS, Novartis, MSD, Roche, Genentech, Astellas, Janssen, Eusa Pharma, Ipsen, Exelixis—Travel Accomodation with Pfizer, BMS, Roche, Astellas, Jannsen, Ipsen. Bayer—Reasonable Honoraria (Talks) from: Pfizer, Roche, Astellas, Novartis, BMS, Janssen Barbara Jereczek Fossa: Travel expenses or speaker fees by Janssen, Ferring, Bayer, Roche, Astellas, Elekta, Carl Zeiss, Ipsen Luigi Da Pozzo: None Giario Natale Conti: Advisor and/or speaker for Janssen, Sanofi, Astellas, Bayer, Ipsen

In the absence of identified therapeutic targets, chemotherapy is the main systemic treatment option for triple-negative breast cancer (TNBC). The achievement of a pathological complete response (pCR) after neoadjuvant chemotherapy leads to good outcome, whereas patients not achieving a pCR are at high risk of relapse. Various trials have evaluated the inclusion of platinum in neoadjuvant chemotherapy regimens for TNBC, leading to non-univocal results. The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on Breast Cancer developed a clinical recommendation on the addition of platinum to anthracycline/taxane-based neoadjuvant chemotherapy for TNBC by using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology and the Evidence to Decision framework (EtD). Five studies were eligible. The panel identified the following outcomes of benefit: pCR (critical), disease/event-free survival (DFS/EFS, critical), and overall survival (OS, critical). The panel identified febrile neutropenia (critical), serious adverse events (critical), anemia grade 3-4 (important), thrombocytopenia grade 3-4 (important) as outcomes of harms. The probability of pCR was higher in the platinum-based chemotherapy group versus control group (RR = 1.45, 95%CI 1.28-1.64); however, no impact on long-term outcome was observed. Neoadjuvant treatment regimens containing platinum resulted in a non-significant increase in the risk of febrile neutropenia and in a significant increase in the risk serious adverse events, G3-G4 anemia and G3-G4 thrombocytopenia: 11.3% versus 0.8%, RR = 15.66 (95%CI 6.38-38.44). The panel judged uncertain/favorable the benefit/harms balance. The panel's final recommendation was conditional in favor of the inclusion of platinum in anthracycline/taxane-based neoadjuvant regimens for TNBC.

Premenopausal women with hormone receptor-positive early breast cancer are candidates for adjuvant endocrine therapy, as recommended by the major international guidelines. To date, adjuvant endocrine options for premenopausal women include tamoxifen with or without ovarian function suppression (OFS) or an aromatase inhibitor with OFS. Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed, and the results of randomised clinical trials have been reported over the last years. Despite this evidence, the optimal algorithm for endocrine therapy for premenopausal women with hormone receptor-positive early stage invasive breast cancer shows open questions regarding the role of OFS in addition to tamoxifen and the optimal use of hormonal agents. The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer applied the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology on three critical questions on the choice of the adjuvant hormonal therapy in premenopausal breast cancer patients to summarise available evidence and to create recommendations to help physicians in their clinical practice., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to record the opinions of Italian oncologists about the use of oral vinorelbine administered metronomically in patients with advanced breast cancer., Methods: A series of meetings were held throughout Italy, and participants were asked how much they agreed with each of the several statements., Results: The majority of oncologists agreed that the concept of the minimum biologically effective dose should be used for drugs administered metronomically. Over 50% agreed that metronomic vinorelbine is an option in first-line chemotherapy for patients with advanced breast cancer, including those with a terminal illness and the elderly, as well as in young and fit patients. Just over one-third of experts agreed that a combination of two chemotherapy agents instead of one is not desirable in metastatic breast cancer because of increased toxicity. Most experts agreed that the main aim of a first-line therapy is to control the disease over time and to preserve quality of life., Conclusion: Metronomically administered oral vinorelbine, either as monotherapy or in combination with other drugs, is effective in the long-term treatment of patients with advanced breast cancer. The clinical profiles of patients should be carefully considered to determine the appropriate treatment strategy.

Background: Conventional pharmacological therapies for the treatment of juvenile idiopathic arthritis (JIA) consist of non-biological, disease-modifying antirheumatic drugs, among which methotrexate (MTX) is the most commonly prescribed. However, there is a lack of consensus-based clinical and therapeutic recommendations for the use of MTX in the management of patients with JIA. Therefore, the Methotrexate Advice and RecommendAtions on Juvenile Idiopathic Arthritis (MARAJIA) Expert Meeting was convened to develop evidence-based recommendations for the use of MTX in the treatment of JIA., Methods: The preliminary executive committee identified a total of 9 key clinical issues according to the population, intervention, comparator, outcome (PICO) approach, and performed an evidence-based, systematic, literature review. During the subsequent Expert Meeting, the relevant evidence was assessed and graded, and 10 recommendations were made., Results: Recommendations relating to the efficacy, optimal dosing and route of administration and duration of treatment with MTX in JIA, and to the issue of folic acid supplementation to prevent MTX side effects, use of MTX in the treatment of chronic JIA-associated uveitis, combination treatment with biologic agents, and the use of vaccinations in patients with JIA were developed. The selected topics were considered to represent clinically important issues facing clinicians caring for patients with JIA. Evidence was insufficient to formulate recommendations for the use of biomarkers predictive of treatment response., Conclusions: These consensus recommendations provide balanced and evidence-based recommendations designed to have broad value for physicians and healthcare clinicians involved in the clinical management of patients with JIA.

In this paper, the results obtained from multivariate statistical techniques such as PCA (Principal component analysis) and LDA (Linear discriminant analysis) applied to a wide soil data set are presented. The results have been compared with those obtained on a groundwater data set, whose samples were collected together with soil ones, within the project "Improvement of the Regional Agro-meteorological Monitoring Network (2004-2007)". LDA, applied to soil data, has allowed to distinguish the geographical origin of the sample from either one of the two macroaeras: Bari and Foggia provinces vs Brindisi, Lecce e Taranto provinces, with a percentage of correct prediction in cross validation of 87%. In the case of the groundwater data set, the best classification was obtained when the samples were grouped into three macroareas: Foggia province, Bari province and Brindisi, Lecce and Taranto provinces, by reaching a percentage of correct predictions in cross validation of 84%. The obtained information can be very useful in supporting soil and water resource management, such as the reduction of water consumption and the reduction of energy and chemical (nutrients and pesticides) inputs in agriculture.

Background: The use of antiangiogenic therapy in non-small cell lung cancer (NSCLC) requires thorough evaluation of patient characteristics in order to avoid potential safety issues, particularly pulmonary haemorrhage (PH). The aim of this consensus by a panel of experts was to identify important criteria for the selection of patients with NSCLC who would benefit from antiangiogenic therapy., Methods: Radiologists and oncologists were selected for the expert panel. The nominal group technique (NGT) and the Delphi questionnaire were used for consensus generation. The NGT consisted of four steps, the result of which was used to set the Delphi questionnaire. A final report was generated based on the opinions of the experts from the panel., Results: An extremely important prerequisite for the evaluation of an antiangiogenic therapeutic approach in patients with NSCLC was thorough clinical and radiological analysis of the relationships between tumour and vascular or anatomical structures (performed in close co-operation by oncologists and radiologists). The panel identified major parameters to be considered before the use of antiangiogenic treatment, collectively agreeing on the relevance of tumour cavitation, vascular infiltration, endobronchial growth and thromboembolism for chest tumour sites, and of the presence of aneurysms, extra-thoracic bleeding, brain metastases or thrombi for extra-thoracic sites. Moreover, a structured report containing information not only on the tumour but also on the general vascular status is essential to guide the treatment choice The experts agreed that tumour localization in the absence of vessel infiltration, cavitation, and the use of antiplatelet therapy are relevant parameters to be assessed, but their presence should not necessarily exclude a patient from receiving antiangiogenic therapy., Conclusion: Close co-operation between oncologists and radiologists in the diagnosis, treatment selection, and assessment of response is essential for ensuring therapeutic appropriateness in the NSCLC setting. It should be noted that neither the use of antiplatelet therapy nor tumour localisation are to be considered as contraindications to antiangiogenic treatment.

Randomized clinical trials are the gold standard to test the efficacy of an intervention within a specified patient population. However, the results of the trials may not be generalizable to routine clinical practice. Observational cohort studies may provide information that complements trial results. Targeted therapies are characterized by tolerability profiles that may differ from those of 'traditional' chemotherapy. Therefore, the post-approval evaluation of these drugs by large, well-designed observational cohort studies in real life populations is warranted. Everolimus is an orally-administered inhibitor of the mammalian target of rapamycin. A number of observational cohort studies have been conducted to characterize the effectiveness and safety of everolimus in clinical practice. In particular, the ORCHIDEE study was designed to identify factors predictive of favorable outcome in patients treated with everolimus such as second-line treatment for metastatic renal cell carcinoma after failure of a first-line treatment with a VEGF TKI. ORCHIDEE is a multicenter, single-arm, phase IV study. The study will enroll approximately 200 metastatic renal cell carcinoma metastatic renal cell carcinoma patients from 20 Italian centers over a 24-month period.

Background: Although data from ongoing trials with targeted agents are awaited, we used a meta-analytical approach to explore whether cytokines (CK), vaccines (VAX), or other therapies may differentially influence patients' outcomes., Materials and Methods: The objective was to determine whether significant interactions exist according to treatment (CK vs. VAX vs. other), in the context of a literature-based meta-analysis. Fourteen trials (3380 patients) were identified, with 10 randomized clinical trials (RCTs) (2257 patients) providing data for the primary outcome--5-year relapse-free survival (RFS). The primary selected end point was 5-year RFS; secondary end points were 5- and 2-year overall survival (OS) and 2-year RFS. Event-based relative risk (RR) ratios with 95% confidence intervals (CI) were extracted and cumulated according to a random-effect model from articles/presentations. Testing for heterogeneity was performed as well., Results: Although not statistically significant, an effect in favor of a qualitative interaction according to treatment was found for 5-year RFS, with a likely detrimental effect in CK (P = .42) in contrast to that found in VAX subpopulation (P = .76). For the secondary end points, a similar effect in favor of a quantitative significant interaction according to treatment was found for 5-year OS, regardless of the approach adopted, with a different magnitude of treatment effect. In addition, a borderline significant (P = .05) detrimental effect in terms of 2-year OS against the use of adjuvant treatment was determined in the CK subpopulation (RR, 1.24; 95% CI, 0.99, 1.54)., Conclusion: The effect in favor of a qualitative interaction according to the adopted strategy is intriguing and suggests potential implications for trial design with targeted agents., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Bacillus Calmette-Guérin and intravesical chemotherapy represent viable adjuvant options for intermediate risk nonmuscle invasive bladder cancer. Although bacillus Calmette-Guérin is perceived as less tolerable than intravesical chemotherapy, to our knowledge no comparative studies have addressed quality of life issues. We compared the quality of life of patients with nonmuscle invasive bladder cancer who received adjuvant intravesical gemcitabine or 1/3 dose bacillus Calmette-Guérin., Materials and Methods: Our multicenter, prospective, randomized, phase II study included 120 patients with intermediate risk nonmuscle invasive bladder cancer. Of these patients 88 remained assessable at 1-year followup. Only 1 patient was withdrawn because of adverse events. Overall 61 patients received 2,000 mg/50 cc gemcitabine weekly for 6 weeks (maintenance monthly for 1 year) while 59 received 1/3 dose bacillus Calmette-Guérin Connaught weekly for 6 weeks (maintenance 3 weekly instillations at 3, 6 and 12 months). Quality of life was measured by the EORTC QLQ-C30 (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3.0) and QLQ-BLS24 (Quality of Life Superficial Bladder Cancer-Specific 24) questionnaires. Group differences were calculated using ANOVA (ANOVA/MANOVA)., Results: Treatment was well tolerated in both groups, although local and systemic side effects were more frequently reported in the bacillus Calmette-Guérin arm. Multivariate analyses showed no significant differences between the 2 groups in all quality of life dimensions. No significant changes over time in quality of life domains were detected for patients on bacillus Calmette-Guérin and gemcitabine except for physical functioning, which decreased significantly in both groups (p = 0.002). No significant differences were detected in terms of recurrence and progression between the 2 groups at 1-year followup., Conclusions: While a higher rate of side effects, albeit mild to moderate, was detected with 1/3 dose bacillus Calmette-Guérin compared to gemcitabine, our study failed to show significant differences between the 2 drugs in terms of quality of life., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)