Paolo Marchetti

Bio: Paolo Marchetti is an academic researcher from Sapienza University of Rome. The author has contributed to research in topics: Breast cancer & Cancer. The author has an hindex of 45, co-authored 497 publications receiving 9210 citations. Previous affiliations of Paolo Marchetti include University of Ferrara & Policlinico Umberto I.

Endocrine side effects induced by immune checkpoint inhibitors

Abstract: Context: In recent years, progress has been made in cancer immunotherapy by the development of drugs acting as modulators of immune checkpoint proteins, such as the cytotoxic T-lymphocyte antigen-4 (CTLA4) and programmed death-1 (PD-1), two co-inhibitory receptors that are expressed on T cells upon activation. These molecules play crucial roles in maintaining immune homeostasis by down-regulating T-cell signaling, thereby preventing unbridled T-cell proliferation while maintaining tolerance to self-antigens, such as tumor-associated antigens. CTLA4 blockade through systemic administration of the CTLA4-blocking antibody ipilimumab was shown to confer significant survival benefit and prolonged stable disease in patients affected by advanced cutaneous melanoma. Other immune checkpoint inhibitors are under clinical evaluation. However, immune checkpoint blockade can lead to the breaking of immune self-tolerance, thereby inducing a novel syndrome of autoimmune/autoinflammatory side effects, designated as “immu...

Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience.

Abstract: OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord. PATIENTS AND METHODS: This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV). RESULTS: We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days. CONCLUSIONS: Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.

A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable

Abstract: Recent evidence suggested a potential correlation between overweight and the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients. We conducted a retrospective study of advanced cancer patients consecutively treated with anti-PD-1/PD-L1 inhibitors, in order to compare clinical outcomes according to baseline BMI levels as primary analysis. Based on their BMI, patients were categorized into overweight/obese (≥ 25) and non-overweight (< 25). A gender analysis was also performed, using the same binomial cut-off. Further subgroup analyses were performed categorizing patients into underweight, normal weight, overweight and obese. Between September 2013 and May 2018, 976 patients were evaluated. The median age was 68 years, male/female ratio was 663/313. Primary tumors were: NSCLC (65.1%), melanoma (18.7%), renal cell carcinoma (13.8%) and others (2.4%). ECOG-PS was ≥2 in 145 patients (14.9%). PD-1/PD-L1 inhibitors were administered as first-line treatment in 26.6% of cases. Median BMI was 24.9: 492 patients (50.6%) were non-overweight, 480 patients (50.4%) were overweight/obese. 25.2% of non-overweight patients experienced irAEs of any grade, while 55.6% of overweight/obese patients (p < 0.0001). ORR was significantly higher in overweight/obese patients compared to non-overweight (p < 0.0001). Median follow-up was 17.2 months. Median TTF, PFS and OS were significantly longer for overweight/obese patients in univariate (p < 0.0001, for all the survival intervals) and multivariate models (p = 0.0009, p < 0.0001 and p < 0.0001 respectively). The significance was confirmed in both sex, except for PFS in male patients (p = 0.0668). Overweight could be considered a tumorigenic immune-dysfunction that could be effectively reversed by ICIs. BMI could be a useful predictive tool in clinical practice and a stratification factor in prospective clinical trials with ICIs.

Prevalence of malnutrition in patients at first medical oncology visit: the PreMiO study

Abstract: // Maurizio Muscaritoli 1 , Simone Lucia 1 , Alessio Farcomeni 2 , Vito Lorusso 3 , Valeria Saracino 3 , Carlo Barone 4 , Francesca Plastino 4 , Stefania Gori 5 , Roberto Magarotto 5 , Giacomo Carteni 6 , Bruno Chiurazzi 6 , Ida Pavese 7 , Luca Marchetti 7 , Vittorina Zagonel 8 , Eleonora Bergo 8 , Giuseppe Tonini 9 , Marco Imperatori 9 , Carmelo Iacono 10 , Luigi Maiorana 10 , Carmine Pinto 11 , Daniela Rubino 11 , Luigi Cavanna 12 , Roberto Di Cicilia 12 , Teresa Gamucci 13 , Silvia Quadrini 13 , Salvatore Palazzo 14 , Stefano Minardi 14 , Marco Merlano 15 , Giuseppe Colucci 16 and Paolo Marchetti 17, 18 , on behalf of the PreMiO Study Group 19 1 Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy 2 Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy 3 Department of Medical Oncology, National Cancer Research Centre Giovanni Paolo II, Bari, Italy 4 Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, Rome, Italy 5 Medical Oncology Unit, Ospedale Sacro Cuore Don Calabria, Verona, Italy 6 Oncology Unit, Antonio Cardarelli Hospital, Naples, Italy 7 Oncology Unit, San Pietro Fatebenefratelli Hospital, Rome, Italy 8 Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy 9 Department of Oncology, University Campus Bio-Medico of Rome, Rome, Italy 10 Department of Medical Oncology, Azienda Ospedaliera Civile - Maria Paterno Arezzo, Ragusa, Italy 11 Medical Oncology, Clinical Cancer Centre, IRCCS-Arcispedale S. Maria Nuova, Reggio Emilia, Italy 12 Department of Oncology-Hematology, Guglielmo da Saliceto Hospital, Piacenza, Italy 13 Medical Oncology Unit, S.S. Trinita Hospital, Sora, Italy 14 Division of Medical Oncology, Mariano Santo Hospital, Azienda Ospedaliera, Cosenza, Italy 15 Medical Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy 16 Medical Oncology Department, National Cancer Research Centre Giovanni Paolo II, Bari, Italy 17 Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology Sapienza, St. Andrea Hospital, Rome, Italy 18 IDI-IRCCS, Rome, Italy 19 The PreMiO Study group also included investigators who contributed to patients’ enrollment Correspondence to: Maurizio Muscaritoli, email: maurizio.muscaritoli@uniroma1.it Keywords: malnutrition, cancer, cachexia, sarcopenia, oncology Received: April 27, 2017 Accepted: June 20, 2017 Published: August 10, 2017 ABSTRACT Background: In cancer patients, malnutrition is associated with treatment toxicity, complications, reduced physical functioning, and decreased survival. The Prevalence of Malnutrition in Oncology (PreMiO) study identified malnutrition or its risk among cancer patients making their first medical oncology visit. Innovatively, oncologists, not nutritionists, evaluated the nutritional status of the patients in this study. Methods: PreMiO was a prospective, observational study conducted at 22 medical oncology centers across Italy. For inclusion, adult patients (>18 years) had a solid tumor diagnosis, were treatment-naive, and had a life expectancy >3 months. Malnutrition was identified by the Mini Nutritional Assessment (MNA), appetite status with a visual analog scale (VAS), and appetite loss with a modified version of Anorexia-Cachexia Subscale (AC/S-12) of the Functional Assessment of Anorexia-Cachexia Therapy (FAACT). Findings: Of patients enrolled ( N= 1,952), 51% had nutritional impairment; 9% were overtly malnourished, and 43% were at risk for malnutrition. Severity of malnutrition was positively correlated with the stage of cancer. Over 40% of patients were experiencing anorexia, as reported in the VAS and FAACT questionnaire. During the prior six months, 64% of patients lost weight (1–10 kg). Interpretation: Malnutrition, anorexia, and weight loss are common in cancer patients, even at their first visit to a medical oncology center.

Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma

Abstract: Background Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Using Multivariate Statistics

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Medscape

Abstract: Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Pembrolizumab versus Ipilimumab in Advanced Melanoma

Abstract: Background The immune checkpoint inhibitor ipilimumab is the standard-of-care treatment for patients with advanced melanoma. Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma. Methods In this randomized, controlled, phase 3 study, we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks. Primary end points were progressionfree and overall survival. Results The estimated 6-month progression-free-survival rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (hazard ratio for disease progression, 0.58; P<0.001 for both pembrolizumab regimens versus ipilimumab; 95% confidence intervals [CIs], 0.46 to 0.72 and 0.47 to 0.72, respectively). Estimated 12-month survival rates were 74.1%, 68.4%, and 58.2%, respectively (hazard ratio for death for pembrolizumab every 2 weeks, 0.63; 95% CI, 0.47 to 0.83; P = 0.0005; hazard ratio for pembrolizumab every 3 weeks, 0.69; 95% CI, 0.52 to 0.90; P = 0.0036). The response rate was improved with pembrolizumab administered every 2 weeks (33.7%) and every 3 weeks (32.9%), as compared with ipilimumab (11.9%) (P<0.001 for both comparisons). Responses were ongoing in 89.4%, 96.7%, and 87.9% of patients, respectively, after a median follow-up of 7.9 months. Efficacy was similar in the two pembrolizumab groups. Rates of treatment-related adverse events of grade 3 to 5 severity were lower in the pembrolizumab groups (13.3% and 10.1%) than in the ipilimumab group (19.9%). Conclusions The anti–PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma. (Funded by Merck Sharp & Dohme; KEYNOTE-006 ClinicalTrials .gov number, NCT01866319.)