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Stefano De Santis,1 Maria Domenica Simone,2 Sebastiano Mercadante,3 Rocco Domenico Mediati,4 Renato Vellucci,4 Paolo Marchetti,5 Giuseppe Tonini,6 Arturo Cuomo,7 Augusto Caraceni,8 Silvia Natoli,9 Grazia Armento,6 Livio Blasi,10 Massimo Mammucari11 On behalf of the IOPS-MS Study Group1Palliative Care and Oncologic Pain Service, S. Camillo-Forlanini Hospital, Rome, Italy; 2Hematology and BMT Unit, S. Camillo-Forlanini Hospital, Rome, Italy; 3Anesthesia and Intensive Care & Pain Relief and Supportive Care, La Maddalena, Palermo, Italy; 4Palliative Care and Pain Therapy Unit, Careggi Hospital, Florence, Italy; 5Molecular and Clinical Medicine Medical Oncology, La Sapienza University of Rome, Rome, Italy; 6Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy; 7Anesthesiology, Resuscitation, and Pain Therapy Department, National Cancer Institute, IRCCS Foundation, Naples, Italy; 8Palliative Care, Pain Therapy and Rehabilitation, National Cancer Institute, IRCCS Foundation, Milan, Italy; 9Department of Clinical Science and Translational Medicine – University of Rome Tor Vergata and Department of Emergency, Admission and Critical Area – Policlinic of Tor Vergata, Rome, Italy; 10Medical Oncology Unit, ARNAS Ospedale Civico Di Cristina Benfratelli, Palermo, Italy; 11Primary Care Unit, ASL RM1, Rome, 00165, ItalyCorrespondence: Stefano De Santis Email sdesantis@scamilloforlanini.rm.itBackground: International guidelines recommend moderate-to-severe cancer pain to be treated with strong opioids. However, pain management remains an unsolved matter, at least in the demanding oncology and palliative care setting. Although cancer pain consists of multiple components, which interact in complex ways where combination therapy can better intercept multiple pain characteristics, few studies have used a non-opioid/opioid association to exploit possible synergistic actions. Even the efforts of a recent approach emphasizing appropriate pain assessment and accurate classification to obtain personalized pain management have not produced a satisfactory analgesic strategy.Objective: This analysis was intended to evaluate the effectiveness of the immediate release fixed combination of oxycodone/acetaminophen (OxyIR/Par) for the treatment of moderate-to-severe intensity background pain used alone or in combination with other strong opioids in cancer patients with breakthrough cancer pain (BTcP). This is a secondary analysis of a wider observational, prospective, multicenter study [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] performed on 179 patients treated with opioids for cancer pain who received the fixed combination of oxycodone/acetaminophen (OxyIR/Par) for the treatment of background pain (BGP).Results: Cancer patients with breakthrough cancer pain and controlled BGP (Background Pain) were classified according to the presence of analgesic therapy with tablets of fixed combination OxyIR/Par alone (group A, n=120) or tablets of fixed combination OxyIR/Par combined with other strong opioids (group B, n=59). Clinical features of group A were different to group B: higher mean Karnofsky Performance Status Index 70.3% (95% CI=67.2– 73.5; median=70, CI=60– 80) vs 58.3 (95% CI=53.4– 63.2; median=50, CI=45– 70) (P< 0.001), and mainly group A patients were treated in an ambulatory setting (55.0% group A vs 33.9% group B) (p< 0.001). Both groups had managed BGP with similar mean dosages (group A: 12.0, CI=10.5– 13.4; group B: 13.1, CI=11.0– 15.1) and frequencies of OxyIR/Par alone for group A and in association to other opioids for group B, but Breakthrough cancer Pain (BTcP) exhibited different characteristics in the two groups, showing a lower mean intensity numerical rating scale (NRS) of 7.5 (95% CI=7.2– 7.7; median=7, CI=7– 8 group A) vs 7.9 (95% CI=7.6, 8.2; median= 8, CI=7– 9 group B) (P=0.04) and a higher percentage of patients had a faster onset, defined as the maximum intensity reached in less than 10 minutes, 81.7% (N=98) in group A vs 59.3% (n=35) in group B (P=0.002).Conclusion: This is the first analysis about the efficacy of an immediate-release fixed combination of OxyIR/Par in the real world for moderate-to-severe background cancer pain and breakthrough cancer pain. The oral fixed combination OxyIR/Par provided an adequate level of analgesia for moderate–severe background cancer pain, in a different cohort of cancer patients with different performance status, both in ambulatory and palliative settings. The low dosage of fixed combination OxyIR/Par was effective alone or in association with other opioids.Keywords: analgesia, combination of oxycodone/acetaminophen, cancer pain, breakthrough cancer pain

Rossella De Luca,1 Livio Blasi,2 Massimiliano Alù,2 Valerio Gristina,1 Giuseppe Cicero1 1Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy; 2Medical Oncology Unit, ARNAS Hospital Civico, Di Cristina, Benfratelli, Palermo, Italy Purpose: Pancreatic carcinoma is the neoplasia with the major mortality, and main standard treatments in this cancer increase survival but do not lead to complete recovery of the patient. The aim of this study was to evaluate the efficacy of Abraxane® (nab-paclitaxel) in Italian patients with metastatic pancreatic cancer (MPC).Patients and methods: We conducted a retrospective analysis of 80 patients. Overall survival (OS) was the primary end point for evaluating the efficacy of nab-paclitaxel in combination with gemcitabine treatment, while carbohydrate antigen 19-9 (CA 19-9) reduction, safety, progression-free survival (PFS), overall response rate and reduction in pain were secondary end points.Results: The median OS was 8 months, and the median PFS was 5 months. A considerable difference in CA 19-9 before and after treatment was observed. Descriptive and correlation analyses were done to examine the relationship between CA 19-9 response and OS. Linear regression analysis between OS and CA 19-9 response revealed that CA 19-9 is an important predictor of OS, showing a positive correlation.Conclusion: Nab-paclitaxel is a well-tolerated and effective treatment for patients affected by MPC. The drug showed an improved tolerability profile, significant pain relief and an increase in survival rate. Keywords: Abraxane, chemotherapy, pancreatic carcinoma, metastasis, CA 19-9, pain, overall survival

Guideline-directed medical therapy (GDMT) of chronic heart failure (HF) associates four drugs: Beta-Blockers (BB), Angiotensin Receptor-Neprilysin Inhibitor (ARNi), Mineralocorticoid Receptor Antagonists (MRA) and Sodium-Glucose co-Transporter 2 (SGLT2) inhibitors. Their initiation and implementation should begin quickly from the diagnostic, but therapeutic inertia leads to higher mortality and hospitalisation rates. To evaluate the feasibility, efficacity and safety of an intensive and fast up-titration program of GDMT at three months, limiting factors to GDMT up-titration and factors associated with poor outcomes in this population. We retrospectively included all patients participating to our up-titration program from January 2021 to September 2022. Patients were followed every 2 weeks by consultation (on-site or teleconsultation). We collected clinic-biological, echocardiographic data and GDMT doses at the enrolment, at the end of the up-titration, and three months later. 222 patients were enrolled. The mean titration duration was 10 weeks (± 57 days). The proportion of patients with full dose of ARNi was 1.4% at day one and 44.6% at three months, 4.5% then 32.7% for MRA, and 5% then 15.4% for BB. 90% of the population was treated with SGLT2 inhibitor at 3 months (Fig. 1). Consecutively, the proportion of patients with loop diuretics decreased from 70.7% to 42.9%. In the meantime, we observed a significant improvement of the dyspnoea (from 85.4% to 45.7% of patient in class II of the NYHA and from 10.8% to 51.1% of patients in class I), the LVEF (from 30.8% to 45.2%) and a decline of the NT-proBNP (from 1322 to 484 pg/ml). Associated adverse events were hypotension (15.3%), acute renal impairment (14.9%) and hyperkalaemia (6.8%) without difference between on-site and teleconsultation groups. Limiting factors to up-titration of ARNi and MRA were advanced age, low eGFR and high value of the NT-proBNP (> 1000 pg/ml). 6 patients died during the study (2.7%) and 16 were readmitted in hospital for HF (7.2%). Persistent treatment with loop diuretics at the end of the up-titration was identified as a poor prognostic, whereas prescription of ARNi was identified as a protective factor. A fast up-titration program is feasible, efficient and safe in real-life practice. Combination of on-site and teleconsultation seems appropriate and should be proposed to fight therapeutic inertia without increasing adverse events. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is associated to a high risk of malnutrition and neoplastic cachexia even at first diagnosis. Malnutrition is a negative prognostic factor for the outcome of surgery or medical oncology treatments. Despite the good awareness of the problem and the knowledge of the guidelines, the early recognition of malnutrition and its management are still uneven, mainly due to the lack of implementation of standardized and shared protocols and the shortage of dedicated clinical nutritionists and dieticians. An early and appropriate nutritional intervention is mandatory to improve the outcome of patients with pancreatic cancer at any stage of disease. The Mini Nutritional Assessment is useful tool to screen patients malnourished or at risk of malnutrition. The need for the establishment and implementation of an integrated hospital - territorial assistance as well as a home-delivered nutrition service is discussed. [ABSTRACT FROM AUTHOR]

Background Nivolumab is an anti-PD-1 antibody that restores the antitumour immune function of T cells, blocking the binding of PD-1 with its ligand PD-L1. PD-1 is expressed on T cells and interacts with PD-L1 on tumour cells. The PD-1-PD-L1 link inhibits T cell activation. In metastatic melanoma, PD-1-PD-L1 binding plays a critical role, and the advent of the immune checkpoint inhibitor nivolumab has delivered new and effective treatment options with proven clinical benefit. In the present study, we evaluated the efficacy of nivolumab in elderly patients with metastatic melanoma. Methods The study enrolled 55 elderly patients (75 years of age and older) with a diagnosis of metastatic melanoma. Primary endpoints of the study were progression-free survival (pfs) and the objective response rate; secondary endpoints were overall survival, reduction in serum lactate dehydrogenase (ldh) from before to after treatment, and tolerability. Results Nivolumab was well tolerated and resulted in good disease control, with a manageable toxicity profile and significant clinical benefit. The duration of pfs was 5.1 months (95% confidence interval: 3.5 months to 6.8 months). A significant correlation was observed between reduction in serum ldh and pfs: 0.60 (95% confidence interval: 0.28 to 0.86; p = 0.002). Conclusions Nivolumab is an immunotherapy treatment that has proved to be an effective and well-tolerated therapeutic option in elderly patients with metastatic melanoma. [ABSTRACT FROM AUTHOR]

Rare samples, such as the Xyloplax specimens collected by the Field Museum in Chicago, have a limited exposure due to their fragility. One solution to widen their exposure is to collect high-resolution, multi-dimensional image data from a single specimen for wide dissemination digitally. A 5 mm by 5 mm Xyloplax specimen has been used to demonstrate this technique. The image dataset was collected in 17 rows and 26 columns with 5 focal point layers for a total of 2,210 images using an automated Philips XL30 ESEM. This data is then tiled and formatted for viewing. Tiled image dataset file sizes commonly reach into the gigapixels (Xyloplax is.68 gigapixels, or 678 megapixels). This size, plus their multi-dimensionality mandate a customized data viewer. We have designed and built a Virtual Scanning Electron Microscope (VSEM) to view these datasets, providing a familiar and intuitive interface based on common scientific instrumentation. The VSEM supports magnification, navigation, and focus adjustment of these large datasets. Just like a scientist using a real SEM, the VSEM gives the investigator freedom to explore any point in the Xyloplax dataset at multiple zoom levels and focal planes. The VSEM has both educational and teaching applications ranging from grade school to the graduate level. Evaluations of students at the high school level have shown that students gain a heightened understanding of scientific instrumentation and data when using the VSEM. After using Virtual Lab students shifted from emotional language and responded to questions using more scientific language. The VSEM can be downloaded for free from http://virtual.itg.uiuc.edu. Teaching tools and assessments can be downloaded from http://edcollege.ucf.edu/nasa/.

Different nanotechnological strategies have been selected to implement biomolecular devices following a bottom-up or top-down approach depending on the biomolecule and on its functionality. Biomolecules have particular functionality and self-assembling capabilities that can be exploited for the implementation of both bioelectronic devices and multipurpose engineered biosurfaces. Surface preparation with supramolecular methods and microcontact printing have been developed and optimised to realise suitable functionalised surfaces. These surfaces can be used to link metalloproteins and enzymes for the implementation of nanobioelectronic devices and planar biosensors or to bind cells in order to promote their growth along predefined tracks and grooves. Some possible applications of these biosurfaces are shown and discussed. Results are presented for the realisation of a biomolecular nanodevice working in air based on the metalloprotein azurin immobilised in the solid state, the formation and characterisation of functional glutamate Dehydrogenase monolayers for nanobiosensing applications, the results of soft lithography processes on azurin for biosensor implementation,and the development of physiological self-assembled patterns of laminin-1 for cell culture applications and hybrid devices. [ABSTRACT FROM AUTHOR]