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Umberto Restelli,1,2 Giovanni Luca Ceresoli,3 Davide Croce,1,2 Laura Evangelista,4 Lorenzo Stefano Maffioli,5 Letizia Gianoncelli,3 Emilio Bombardieri6 1Center for Health Economics, Social and Health Care Management, LIUC – Università Cattaneo, Castellanza, Italy; 2School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 3Medical Oncology Department, Thoracic and Urologic Oncology Unit, Cliniche Humanitas Gavazzeni, Bergamo, 4Nuclear Medicine and Molecular Imaging Unit, Veneto Institute of Oncology IOV – IRCCS, Padova, 5Nuclear Medicine Department, Cancer Centre – ASST Ovest Milanese, Legnano, 6Nuclear Medicine Department, Cliniche Humanitas Gavazzeni, Bergamo, Italy Background: Prostate cancer (PCa) accounts for 20% of all cancers in subjects over 50 years in Italy. The majority of patients with PCa present with localized disease at the time of diagnosis, but many patients develop recurrent metastatic disease after treatment with curative intent. Androgen deprivation therapy is the standard of care for metastatic PCa patients; unfortunately, most of them progress to castrate-resistant prostate cancer (CRPC) within 5 years. Metastatic CRPC (mCRPC) heavily affects patients in terms of quality of life, side effects, and survival, and greatly impacts economic costs. The approval of new effective agents in recent years, including cabazitaxel, abiraterone acetate, enzalutamide, and radium-223, has dramatically changed patient management.Materials and methods: Here, we aimed to estimate the current costs of illness of mCRPC in Italy. All patients affected by mCRPC and treated with a single agent in an annual time horizon were considered. Therefore, the analysis was not focused on the management pathway of single patients through different lines of treatment. Direct medical costs referred to therapy, adverse event management, and skeletal-related event management were analyzed. A bottom-up approach was used to estimate the resource consumption: through national guidelines and expert opinions, the mean cost per patient was estimated and then multiplied by the total number of patients diagnosed with mCRPC. Results: Direct medical costs ranged from €196.5 million to €228.0 million, representing ~0.2% of the financing of the Italian National Health Service in 2016. The main cost driver was the cost of treatment, which represented more than 77% of the overall economic burden.Conclusion: Our analysis, reflective of real clinical practice, shows for the first time the high economic cost of mCRPC in Italy. Keywords: metastatic castrate-resistant prostate cancer, cost analysis, resource consumption, Italy, skeletal related events, oncology

Restelli U, Ceresoli GL, Croce D et al. Economic burden of the management of metastatic castrate-resistant prostate cancer in Italy: a cost of illness study. Cancer Management and Research. 2017;9:789–800.On page 796, above the Disclosure section, the Acknowledgment section is missing. The missing text is:AcknowledgmentThe authors thank Ray Hill, an independent medical writer, who provided English-language editing and journal styling prior to submission on behalf of Health Publishing & Services Srl. Editorial support was funded through an unconditional contribution by Bayer SpA.Read the original article.

Background: To date, only a few studies reported data regarding the development of mucosal immune response after the BNT162b2-booster vaccination., Methods: Samples of both serum and saliva of 50 healthcare workers were collected at the day of the booster dose (T3) and after two weeks (T4). Anti-S1-protein IgG and IgA antibody titres and the neutralizing antibodies against the Wuhan wild-type Receptor-Binding Domain in both serum and saliva were measured by quantitative and competitive ELISA, respectively. Data were compared with those recorded after the primary vaccination cycle (T2). Neutralizing antibodies against the variants of concern were measured in those individuals with anti-Wuhan neutralizing antibodies in their saliva., Findings: After eight months from the second dose, IgG decreased in both serum (T2 GMC : 23,838.5 ng/ml; T3 GMC : 1473.8 ng/ml) and saliva (T2 GMC : 12.9 ng/ml; T3 GMC : 0.3 ng/ml). Consistently, serum IgA decreased (T2 GMC : 48.6 ng/ml; T3 GMC : 6.4 ng/ml); however, salivary IgA showed a different behaviour and increased (T2 GMC : 0.06 ng/ml; T3 GMC : 0.41 ng/ml), indicating a delayed activation of mucosal immunity. The booster elicited higher titres of both IgG and IgA when compared with the primary cycle, in both serum (IgG T4 GMC : 98,493.9 ng/ml; IgA T4 GMC : 187.5 ng/ml) and saliva (IgG T4 GMC : 21.9 ng/ml; IgA T4 GMC : 0.65 ng/ml). Moreover, the booster re-established the neutralizing activity in the serum of all individuals, not only against the Wuhan wild-type antigen (N = 50; INH: 91.6%) but also against the variants (Delta INH: 91.3%; Delta Plus INH: 89.8%; Omicron BA.1 INH: 85.1%). By contrast, the salivary neutralizing activity was high against the Wuhan antigen in 72% of individuals (N = 36, INH: 62.2%), but decreased against the variants, especially against the Omicron BA.1 variant (Delta N = 27, INH: 43.1%; Delta Plus N = 24, INH: 35.2%; Omicron BA.1 N = 4; INH: 4.7%). This was suggestive for a different behaviour of systemic immunity observed in serum with respect to mucosal immunity described in saliva (Wald chi-square test, 3 df of interaction between variants and sample type = 308.2, p < 0.0001)., Interpretation: The BNT162b2-booster vaccination elicits a strong systemic immune response but fails in activating an effective mucosal immunity against the Omicron BA.1 variant., Funding: This work was funded by the Department of Medicine and Surgery, University of Insubria, and supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020), Italy., Competing Interests: Declaration of interests None to declare., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Although the BNT162b2 COVID-19 vaccine is known to induce IgG neutralizing antibodies in serum protecting against COVID-19, it has not been studied in detail whether it could generate specific immunity at mucosal sites, which represent the primary route of entry of SARS-CoV-2., Methods: Samples of serum and saliva of 60 BNT162b2-vaccinated healthcare workers were collected at baseline, two weeks after the first dose and two weeks after the second dose. Anti-S1-protein IgG and IgA total antibodies titres and the presence of neutralizing antibodies against the Receptor Binding Domain in both serum and saliva were measured by quantitative and by competitive ELISA, respectively., Findings: Complete vaccination cycle generates a high serum IgG antibody titre as a single dose in previously infected seropositive individuals. Serum IgA concentration reaches a plateau after a single dose in seropositive individuals and two vaccine doses in seronegative subjects. After the second dose IgA level was higher in seronegative than in seropositive subjects. In saliva, IgG level is almost two orders of magnitude lower than in serum, reaching the highest values after the second dose. IgA concentration remains low and increases significantly only in seropositive individuals after the second dose. Neutralizing antibody titres were much higher in serum than in saliva., Interpretation: The mRNA BNT162b2 vaccination elicits a strong systemic immune response by drastically boosting neutralizing antibodies development in serum, but not in saliva, indicating that at least oral mucosal immunity is poorly activated by this vaccination protocol, thus failing in limiting virus acquisition upon its entry through this route., Funding: This work was funded by the Department of Medicine and Surgery, University of Insubria, and partially supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020)., Competing Interests: Declaration of interests None to declare., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The use of robotics is becoming widespread in healthcare. However, little is known about how robotics can affect the relationship with patients during an emergency or how it impacts clinicians in their organization and work. As a hospital responding to the consequences of the COVID-19 pandemic "ASST dei Sette Laghi" (A7L) in Varese, Italy, had to react quickly to protect its staff from infection while coping with high budgetary pressure as prices of Personal Protection Equipment (PPE) increased rapidly. In response, it introduced six semi-autonomous robots to mediate interactions between staff and patients. Thanks to the cooperation of multiple departments, A7L implemented the solution in less than 10 weeks. It reduced risks to staff and outlay for PPE. However, the characteristics of the robots affected staff's perceptions. This case study reviews critical issues faced by A7L in introducing these devices and recommendations for the path forward.

Importance: Since February 2020, coronavirus disease 2019 (COVID-19) has spread rapidly all over the world, with an epidemiological cluster in Lombardy, Italy. The viral communicability may be mediated by various body fluids, but insufficient information is available on the presence of the virus in human tears., Objectives: To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears collected from patients with COVID-19 by means of real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay and to assess the association of virus presence with concomitant clinical conditions., Design, Setting, and Participants: Cross-sectional study conducted between April 9 and May 5, 2020. The setting was intensive care units at Azienda Socio-Sanitaria Territoriale (ASST) Sette-Laghi Hospital, University of Insubria, in Varese, Lombardy, Italy. A conjunctival swab was performed in 91 patients hospitalized for COVID-19, which was clinically diagnosed by rRT-PCR assay on nasopharyngeal swabs and by radiological imaging. Conjunctival swabs from 17 additional healthy volunteer participants with no symptoms of COVID-19 were examined to evaluate the availability and applicability of the conjunctival swab test., Exposure: SARS-CoV-2 detection by means of rRT-PCR assay performed on the collected samples obtained by conjunctival swabs., Main Outcomes and Measures: Conjunctival swab and nasopharyngeal swab results are reported, as well as demographic and clinical data., Results: A total of 108 participants (mean [SD] age, 58.7 [14.2] years; 55 female and 53 male) were tested for SARS-CoV-2 using rRT-PCR assay, including 91 patients hospitalized with COVID-19 and 17 were healthy volunteers. SARS-CoV-2 was found on the ocular surface in 52 of 91 patients with COVID-19 (57.1%; 95% CI, 46.3%-67.5%), with a wide variability in the mean viral load from both eyes. Among a subset of 41 patients, concordance of 63.0% (95% CI, 41.0%-81.0%) was found between positive conjunctival and nasopharyngeal swab test results when performed within 2 days of each other. In 17 of these patients, nasopharyngeal swab results were negative for SARS-CoV-2. In 10 of these 17 patients, conjunctival swab results were positive for the virus., Conclusions and Relevance: In this study, SARS-CoV-2 RNA was found on the ocular surface in a large part of this cohort of patients with COVID-19, although the infectivity of this material could not be determined. Because patients may have positive test results with a conjunctival swab and negative results with a nasopharyngeal swab, use of the slightly invasive conjunctival swab may be considered as a supplementary diagnostic test.

The onset of skeletal metastases is typical of advanced-stage prostate cancer and requires a multidisciplinary approach to alleviate bone pain and try to delay disease progression. The current therapeutic armamentarium includes conventional analgesics, chemotherapeutic agents, immunotherapy, androgen-deprivation therapy, osteoclast inhibitors (bisphosphonates, denosumab), surgical interventions, external-beam radiotherapy and radionuclide metabolic therapy. Many studies in recent decades have demonstrated the efficacy of various radiopharmaceuticals, including strontium-89 and samarium-153, for palliation of pain from diffuse skeletal metastases, but no significant benefit in terms of disease progression and overall survival has been shown. The therapeutic landscape of metastatic skeletal cancer significantly changed after the introduction of radium-223, the first bone-homing radiopharmaceutical with disease-modifying properties. In this paper we extensively review the literature on the use of radium-223 dichloride in metastatic castration-resistant prostate cancer.

The usefulness of I-ioflupane imaging for detecting loss of functional dopaminergic neuron terminals in the striatum of patients with clinically uncertain parkinsonian syndromes is well known, especially to differentiate essential tremor from parkinsonisms. Here we present a case of a patient suspected of essential tremor but not responding to standard therapy, in which the results of DaTscan were fundamental to set up an alternative therapeutic approach.

Purpose: The aim of this study was to analyse if the result of a baseline (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan, in large-vessel vasculitis (LVV) patients, is able to predict the course of the disease, not only in terms of presence/absence of final complications but also in terms of favourable/complicated progress (response to steroid therapy, time to steroid suspension, relapses, etc.)., Methods: A total of 46 consecutive patients, who underwent (18)F-FDG PET/CT between May 2010 and March 2013 for fever of unknown origin (FUO) or suspected vasculitis (before starting corticosteroid therapy), were enrolled. The diagnosis of LVV was confirmed in 17 patients. Considering follow-up results, positive LVV patients were divided into two groups, one characterized by favourable (nine) and the other by complicated progress (eight), on the basis of presence/absence of vascular complications, presence/absence of at least another positive PET/CT during follow-up and impossibility to comply with the tapering schedule of the steroid due to biochemical/symptomatic relapse. Vessel uptake in subjects of the two groups was compared in terms of intensity and extension. To evaluate the extent of active disease, we introduced two volume-based parameters: "volume of increased uptake" (VIU) and "total lesion glycolysis" (TLG). The threshold used to calculate VIU on vessel walls was obtained by the "vessel to liver" ratio by means of receiver-operating characteristic analysis and was set at 0.92 × liver maximum standardized uptake value in each patient., Results: Measures of tracer uptake intensity were significantly higher in patients with complicated progress compared to those with a favourable one (p < 0.05). Measures of disease extension were even more significant and TLG emerged as the best parameter to separate the two groups of patients (p = 0.01)., Conclusion: This pilot study shows that, in LVV patients, the combined evaluation of the intensity and the extension of FDG vessel uptake at diagnosis can predict the clinical course of the disease, separating patients with favourable or complicated progress.

We evaluated the clinical usefulness of single-photon emission tomography (SPET) with technetium-99m sestamibi and indium-111 pentetreotide in breast cancer staging. Fifteen patients with clinical and/or mammographic findings suggesting T1-2N0-1 breast cancer were studied. SPET images were acquired 20 min after 99mTc-sestamibi injection and 4 and 24 h after 111In-pentetreotide injection. Patients underwent surgery the day after the later 111In-pentetreotide acquisition. Pathological examination showed 16 tumours in the 15 patients, with one bilateral carcinoma. The mean tumour diameter was 18.7 mm. Metastatic axillary involvement was found in 6/16 tumours, with a mean of five metastatic nodes per axilla. Both tracers correctly identified 15/16 primary tumours and five of the six cases of metastatic axillary node involvement. No difference between the tracers was observed in breast cancer staging. 99mTc-sestamibi seems to be the better tracer in terms of physical characteristics, execution time and cost-effectiveness. Our data suggest the future possibility of using nuclear medicine imaging to avoid axillary dissection in patients with T1 breast cancer.

Unlabelled: This study evaluated the clinical role of SPECT with sestamibi versus CT in the presurgical staging of lung cancer., Methods: Forty-seven consecutive patients (44 men, 3 women; mean age 63.3 yr, range 49-82 yr) with clinical and radiological suspicion of lung cancer were enrolled in this study. Staging procedures including radiography, CT, fiberoptic bronchoscopy and sestamibi SPECT of the thorax. Radionuclide imaging was performed after intravenous injection of 740-925 MBq of sestamibi. In 36 patients a histological diagnosis was made, and these patients were evaluated for the study of mediastinal lymph node involvement., Results: Mediastinal lymph node involvement was demonstrated in 11 of the 36 patients evaluated. Sestamibi SPECT correctly staged 10 of 11 patients with and 21 of 25 without mediastinal nodes, showing a diagnostic sensitivity of 91% and a specificity of 84%. Computed tomography gave 8 true-positive and 15 true-negative results, with a sensitivity of 73% and a specificity of 60%. Sestamibi SPECT results were also better than those of CT with regard to positive and negative predictive values and accuracy., Conclusion: The clinical role of sestamibi SPECT can be fully appreciated when the technique is used in selected patients, combined with CT or MRI, or both, to assess mediastinal involvement and avoid any invasive staging procedures.

Background: A residual mediastinal mass after treatment represents a common diagnostic problem in the management of patients with Hodgkin lymphoma (HD). Conventional diagnostic radiology, computed tomography (CT), or ultrasonography (US) do not adequately reflect changes as fibrosis or necrosis. Gallium-67 (67Ga) imaging has been proven to be useful for the evaluation of HD in the mediastinum. The authors compared the ability of gallium scan and magnetic resonance imaging (MRI) to evaluate the mediastinal disease in the follow-up of patients with HD., Methods: Thirty-four patients previously treated for HD were investigated with gallium scan, MRI, and all the other investigations to evaluate the mediastinal region. Sixteen patients were in restaging after treatment, and 18 were investigated for suspected radiologic recurrence in the mediastinum (follow-up, 9-75 months). The results of gallium scan and MRI were matched with clinical findings during the follow-up., Results: A sensitivity of 85.7% for 67Ga and 92.8% for MRI was found, while the specificity was 100% for the scan and 80.6% for MRI. The predictive positive value that resulted was 100% for 67Ga and 68.4% for MRI., Conclusions: Both examinations were accurate in assessing the activity of residual masses in the mediastinum after treatment. 67Ga showed a lower sensitivity in comparison with MRI, but 67Ga frequently overestimates the presence of pathologic tissue. The authors acknowledge the complementary role of these two tests, but if only one of these examinations can be performed for logistic or economic reasons, then gallium scan represents the single most adequate diagnostic procedure.

In this report we describe our experience with [123I]IBZM ([123I]-(S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolid inyl)methyl] benzamide), used to image the lesions in a female patient affected by metastatic melanoma. Marked uptake of [123I]IBZM in an area corresponding to a palpable lymph-nodal mass was observed in images collected 2 and 5 hours after i.v. tracer administration. Tumour to non-tumour ratios evaluated on planar maps were found to be 2.04 and 2.35, respectively. Surgical excision and histological examination of inguinal nodes confirmed the presence of melanoma lymph-nodal metastases. Although scintigraphy with radiolabelled [123I]IBZM is widely used for neuro-psychiatric disorders, we have found no reports in the literature of any application of this tracer in oncology. Even if the biological bases underlying the findings reported here remain unclear (although they are probably related to the neural crest origin of the melanocytes), the quality of imaging found suggests that this tracer may provide a new diagnostic tool for the imaging of melanoma tumours.