Impact of the environment on the health: From theory to practice.

The Erice 56 Charter titled "Impact of the environment on the health: from theory to practice" was unanimously approved at the end of the 56th course of the "International School of Epidemiology and Preventive Medicine G. D'Alessandro" held from 3rd to November 7, 2019 in Erice - Sicily (Italy) and promoted by the Study Group of "Environment and Health" of the Italian Society of Hygiene, Preventive Medicine and Public Health. The course, that included lectures, open discussions and guided working groups, was aimed to provide a general training on epidemiological and toxicological aspects of the environmental health impact, to be used by public health professionals for risk assessment, without forgetting the risk communications. At the end of the course 12 key points were agreed among teachers and students: they underlined the need of specific training and research, in the perspective of "One Health" and "Global Health", also facing emerging scientific and methodological issues and focusing on communication towards stakeholders. This Discussion highlight the need to improve knowledge of Health and Environment topic in all sectors of health and environmental prevention and management.

Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma.

BACKGROUND: The phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We report updated efficacy data from the second interim analysis. PATIENTS AND METHODS: Treatment-naive patients with aRCC were randomized (1 : 1) to receive avelumab (10 mg/kg) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were PFS and overall survival (OS) among patients with programmed death ligand 1-positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population. RESULTS: Of 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm {PD-L1+ population: hazard ratio (HR) 0.62 [95% confidence interval (CI) 0.490-0.777]}; one-sided P < 0.0001; median 13.8 (95% CI 10.1-20.7) versus 7.0 months (95% CI 5.7-9.6); overall population: HR 0.69 (95% CI 0.574-0.825); one-sided P < 0.0001; median 13.3 (95% CI 11.1-15.3) versus 8.0 months (95% CI 6.7-9.8)]. OS data were immature [PD-L1+ population: HR 0.828 (95% CI 0.596-1.151); one-sided P = 0.1301; overall population: HR 0.796 (95% CI 0.616-1.027); one-sided P = 0.0392]. CONCLUSION: Among patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature. CLINICAL TRIAL NUMBER: NCT02684006.

Ocrelizumab in a case of refractory chronic inflammatory demyelinating polyneuropathy with anti-rituximab antibodies.

Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, has demonstrated good efficacy as treatment in patients with resistant chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but it is highly immunogenic due to its structure. Ocrelizumab (OCR) is a humanized anti-CD20 antibody, with higher tolerability and a lower immunogenic profile compared to RTX. We present a case of refractory CIDP effectively treated with OCR, switched from RTX after the development of anti-drug antibodies. A 25-year-old man was admitted to our clinic for the onset of distal upper and lower limb weakness and numbness, with electrodiagnostic criteria of CIDP. After several attempted standard CIDP treatments, RTX was introduced due to poor control of clinical relapses. Unfortunately, the patient developed a high anti-drug antibody titer after RTX infusion, with no control of disease. OCR was started as an off-label treatment, resulting in partial recovery from the last recurrence and achieving good prevention of new relapses with no adverse events. We suggest that OCR should be considered as another therapeutic option in refractory CIDP. In the literature, this is the first case of CIDP treated with OCR, demonstrating good efficacy for its anti-CD20 effect and better tolerability because of its lower immunogenicity.

Health conditions of migrants landed in north-eastern Sicily and perception of health risks of the resident population.

OBJECTIVES: In Italy, a recent irregular movement of people raised concerns among the host population on possible introduction of diseases that have long been controlled in the host countries. This study evaluates the health conditions of illegal immigrants landed on the north-eastern Sicilian territory, to provide information on the clinical and epidemiologic burden of infectious diseases among migrants and how the local population feel about these landings. STUDY DESIGN: The study design is a cross-sectional study. METHODS: The study considered all migrants landed illegally in the city of Messina, Sicily, between January 2014 and July 2018. Analysing the data of hospital admissions and disease notifications, we calculated the frequency of infectious diseases among migrant population. Furthermore, through a survey conducted by a well-known online newspaper, we analysed the perception that the local population has about the health risk represented by migrants. RESULTS: In the considered five-year period, 108 landings, for a total of 38,608 migrants occurred at the Messina port. The percentage of hospitalisation was rather low (3.5%), and it concerned mainly pregnant women. The notifications of infectious diseases were contained, with exception of scabies and tuberculosis. Finally, from the online survey, resulted that there is a large part of local population that considers migrants a potential danger to community health. CONCLUSIONS: Our data show that the presence of migrants should not have to date any impact on the health conditions of the resident population. However, monitoring over time the health of migrants and screening for infectious diseases as soon as possible after landing are advantageous for both migrants and host country.

Today's vaccination policies in Italy: The National Plan for Vaccine Prevention 2017-2019 and the Law 119/2017 on the mandatory vaccinations.

The National Plan for Vaccine Prevention 2017-2019 has expanded the vaccination offer including new vaccines, enlarging the target population and introducing for the first time in Italy a life-course approach to vaccination. A "lifetime immunization schedule" is aimed to reduce the burden and the related costs of vaccine-preventable diseases through effective vaccination programs. However, to counteract the national steady downward trend in the uptake of vaccinations that caused a drop of the vaccination coverage below the 95% threshold to allow herd immunity, it was decided to make 10 vaccinations mandatory by the law 119/2017. In particular, in addition to already mandatory vaccinations against diphtheria, tetanus, hepatitis B and poliomyelitis, those against measles, mumps, rubella (MMR), varicella, pertussis and Haemophilus influenzae type b (Hib) were added to the list. According to the law, all unvaccinated children cannot attend preschool services until the age of 6 years and fines (from 100 to 500 Euros) are provided for parents. Moreover, this law provided, in its first application, a catch-up campaign for children up to the age of 16 years and the free-of-charge offer of all mandatory and recommended vaccines to each child not yet vaccinated according to the previous NPVP. The NPVP includes also several at risk categories, such as pregnant women, healthcare workers and subjects suffering from chronic diseases, to whom specific vaccinations, free of charge, are offered. The vaccinations of pregnant women have different purposes. In order to decrease the pertussis risk in newborns in the first months of life, a booster immunization of DTPa is recommended, at every pregnancy, between week 27th and 36th. Instead, the influenza vaccine administration to pregnant women during the second or third quarter is mainly aimed to avoid the risk of serious disease complications for both the mother and the fetus. Another group of at risk subjects included in the NPVP is that made up by healthcare workers. According to the plan, "an adequate immunization of the healthcare workers is essential for the prevention and control of infections (anti-hepatitis B, anti-influenza, anti-measles-mumps-rubella, anti-varicella, anti-pertussis)". Finally, almost all the vaccinations foreseen by the NPVP are offered free of charge to subjects suffering from specific diseases. These include cardiovascular, respiratory, hepatic, neoplastic, renal and metabolic disorders, in addition to immunosuppression that exposes them to an increased risk of contracting invasive infectious diseases.

Measles outbreak from February to August 2017 in Messina, Italy.

INTRODUCTION: Measles continues to be a major public health issue worldwide, with high morbidity and mortality rates. The disease remains endemic in 14 European countries, including Italy where, from 2013 to 2016, over 5,000 cases have been reported. In 2017, many Italian regions, including Sicily, have reported many cases of measles. In this study, we described the latest measles outbreak in the city of Messina, from 1st February to 31st August 2017. METHODS: We considered all reported measles cases that came to the "Public Health, Epidemiology and Preventive Medicine" Operative Unit of the Messina Provincial Health Agency Prevention Department, which receives all reported cases of measles in the Messina province. RESULTS: From 1st February to 31st August 2017, a total of 59 measles cases were reported, of which 44 were confirmed, nine were classified as possible, four were probable and two cases were discarded. Of the 57 possible, probable and confirmed cases, 31 (54%) were males and 26 (46%) were females. Moreover, 54 (95%) had not been previously vaccinated while the remaining cases had documented evidence of one (two cases) or two doses (one case). Genotype B3 was identified in 39/44 cases (88,6%) by the regional reference laboratory in Palermo. CONCLUSIONS: Despite the development of an effective vaccination, unfortunately measles continues to threaten the lives of millions of children worldwide each year. The suboptimal immunization level in Italy has led to an increase in the transmission of measles with detrimental effects on both public health and ongoing measles elimination efforts.

Herpes zoster vaccine: a protection for the elderly.

The Herpes Zoster vaccine is strongly recommended by the World Health Organization to promote healthy aging by preventing the corresponding age- related disease, also named shingles. The disease is due to the endogenous reactivation of Varicella Zoster Virus, the causal agent of chickenpox, that becomes latent at the peripheral nervous system level. Here, owing to the host's cell-mediated immunity, it may be confined for several decades. However, the immune senescence allows the possibility of virus reactivation, causing the onset of neuropathic pain and skin rash that characterize the acute disease. Sometimes, the neuralgia becomes chronic causing postherpetic neuralgia that has a significant impact on the quality of patient life, analogously to the ophthalmic HZ, a particularly feared form of disease. Due to the causal relationship between decreasing immune defenses and virus reactivation with disease onset, the incidence of Herpes Zoster, in Italy now equal to 6.42 (95%CI: 5.93-6.95) cases per 1,000 people per year will increase steadily in the future due to the longevity rise of the population. Considering epidemiological impact, complications and sequelae in the short- and long-term, costs of clinical-therapeutical management of patients, and, above all, the poor effectiveness of available therapy the only effective intervention is vaccination of the elderly. Currently in the European Union, there is only one vaccine for Herpes Zoster prevention, formed by live attenuated OKA-Merck virus strain that is also used for paediatric vaccine. According to the Health Technology Assessment surveys, the intervention cost (based on "Quality Adjusted Life Years") is clearly below the discriminating threshold value to judge the feasibility and, as predicted by the Italian National Plan of Vaccinal Prevention 2017-2019, the vaccine is offered free to all subjects >65 years.

Scattering of the Halo Nucleus

Angular distributions of the elastic, inelastic, and breakup cross sections of the halo nucleus ^{11}Be on ^{197}Au were measured at energies below (E_{lab}=31.9 MeV) and around (39.6 MeV) the Coulomb barrier. These three channels were unambiguously separated for the first time for reactions of ^{11}Be on a high-Z target at low energies. The experiment was performed at TRIUMF (Vancouver, Canada). The differential cross sections were compared with three different calculations: semiclassical, inert-core continuum-coupled-channels and continuum-coupled-channels ones with including core deformation. These results show conclusively that the elastic and inelastic differential cross sections can only be accounted for if core-excited admixtures are taken into account. The cross sections for these channels strongly depend on the B(E1) distribution in ^{11}Be, and the reaction mechanism is sensitive to the entanglement of core and halo degrees of freedom in ^{11}Be.

The linker region of breast cancer resistance protein ABCG2 is critical for coupling of ATP-dependent drug transport.

The ATP-binding cassette (ABC) transporters of class G display a different domain organisation than P-glycoprotein/ABCB1 and bacterial homologues with a nucleotide-binding domain preceding the transmembrane domain. The linker region connecting these domains is unique and its function and structure cannot be predicted. Sequence analysis revealed that the human ABCG2 linker contains a LSGGE sequence, homologous to the canonical C-motif/ABC signature present in all ABC nucleotide-binding domains. Predictions of disorder and of secondary structures indicated that this C2-sequence was highly mobile and located between an α-helix and a loop similarly to the C-motif. Point mutations of the two first residues of the C2-sequence fully abolished the transport-coupled ATPase activity, and led to the complete loss of cell resistance to mitoxantrone. The interaction with potent, selective and non-competitive, ABCG2 inhibitors was also significantly altered upon mutation. These results suggest an important mechanistic role for the C2-sequence of the ABCG2 linker region in ATP binding and/or hydrolysis coupled to drug efflux.

Epidemiological HIV infection surveillance among subjects with risk behaviours in the city of Messina (Sicily) from 1992 to 2015.

INTRODUCTION: Epidemiological studies are a key element in determining the evolution and spread of HIV infection among the world population. Knowledge of the epidemiological dynamics improves strategies for prevention and monitoring. METHODS: We examined 2,272 subjects who voluntarily underwent HIV testing from January 1992 to December 2015. For each subject, an anonymous form was completed to obtain information on personal data, sexual habits and exposure to risk factors. RESULTS: The number of subjects undergoing the screening test has increased over the years and the average age of the tested subjects has decreased over time. The main motivation for undergoing HIV testing is unprotected sex. Although heterosexual subjects taking the test were more numerous than homosexuals in this study, an increase in the latter over time should be highlighted. CONCLUSIONS: Although the number of tests performed has increased over the years, the persistence of unprotected sex shows an inadequate perception of risk. Therefore, it is necessary to implement programmes to increase the general awareness of HIV infection. It is also essential to undertake constant monitoring of behaviour, risk perception and the application of the screening test via surveillance systems in order to implement effective and efficient prevention.

Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness.

H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease.

Antibacterial activity of nanoparticles and nanomaterials: a possible weapon in the fight against healthcare-associated infections.

Healthcare-associated infections are a serious threat in terms of morbidity and mortality for all patients receiving healthcare. The problem is aggravated by the increasingly widespread phenomenon of antibiotic resistance, with some microorganisms now resistant to all or almost all the currently available antibiotics. Nanomaterials are compounds used by many different industrial fields and they are currently studied for their intrinsic antimicrobial properties. To date, many researchers have considered using many different nanoparticles and nanomaterials to produce surfaces and medical devices with intrinsic antimicrobial features. Many compounds have shown very interesting and effective antimicrobial capacities and could be used, in the future, to manufacture new hospital surfaces and medical devices. However, many studies have to be carried out to evaluate the effective potential use of these compounds. The aim of this paper is to review the main literature regarding this topic, focusing on the main types of nanoparticles and nanomaterials studied for this purpose.

Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma.

BACKGROUND: We report updated data for avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma from the third interim analysis of the phase III JAVELIN Renal 101 trial. PATIENTS AND METHODS: Progression-free survival (PFS), objective response rate (ORR), and duration of response per investigator assessment (RECIST version 1.1) and overall survival (OS) were evaluated in the overall population and in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups; safety was also assessed. RESULTS: Overall, median OS [95% confidence interval (CI)] was not reached [42.2 months-not estimable (NE)] with avelumab plus axitinib versus 37.8 months (31.4-NE) with sunitinib [hazard ratio (HR) 0.79, 95% CI 0.643-0.969; one-sided P = 0.0116], and median PFS (95% CI) was 13.9 months (11.1-16.6 months) versus 8.5 months (8.2-9.7 months), respectively (HR 0.67, 95% CI 0.568-0.785; one-sided P < 0.0001). In patients with IMDC favorable-, intermediate-, poor-, or intermediate plus poor-risk disease, respectively, HRs (95% CI) for OS with avelumab plus axitinib versus sunitinib were 0.66 (0.356-1.223), 0.84 (0.649-1.084), 0.60 (0.399-0.912), and 0.79 (0.636-0.983), and HRs (95% CIs) for PFS were 0.71 (0.490-1.016), 0.71 (0.578-0.866), 0.45 (0.304-0.678), and 0.66 (0.550-0.787), respectively. ORRs, complete response rates, and durations of response favored avelumab plus axitinib overall and across all risk groups. In the avelumab plus axitinib arm, 81.1% had a grade ≥3 treatment-emergent adverse event (TEAE), and incidences of TEAEs and immune-related AEs were highest <6 months after randomization. CONCLUSIONS: Avelumab plus axitinib continues to show improved efficacy versus sunitinib and a tolerable safety profile overall and across IMDC risk groups. The OS trend favors avelumab plus axitinib versus sunitinib, but data remain immature; follow-up is ongoing. TRIAL REGISTRATION: ClinicalTrials.govNCT02684006; https://clinicaltrials.gov/ct2/show/NCT02684006.

Efficacy of avelumab plus axitinib versus sunitinib by numbers of IMDC risk factors and target tumor sites at baseline in advanced renal cell carcinoma: long-term follow-up results from JAVELIN Renal 101.

BACKGROUND: In the phase III JAVELIN Renal 101 trial, first-line avelumab + axitinib improved progression-free survival (PFS) and objective response rate versus sunitinib in patients with advanced renal cell carcinoma across all International Metastatic RCC Database Consortium (IMDC) risk groups (favorable, intermediate, and poor); analyses of overall survival (OS) remain immature. Here, we report post hoc analyses of efficacy from the third interim analysis (data cut-off, April 2020) by the numbers of IMDC risk factors and target tumor sites at baseline. METHODS: Efficacy endpoints assessed were PFS, objective response, and best overall response per investigator assessment (RECIST v1.1) and OS. Best percentage change and percentage change from baseline in target tumor size over time during the study were also assessed. RESULTS: In patients with 0, 1, 2, 3, or 4-6 IMDC risk factors, hazard ratios [HRs; 95% confidence interval (CIs)] for OS with avelumab + axitinib versus sunitinib were 0.660 (0.356-1.223), 0.745 (0.524-1.059), 0.973 (0.668-1.417), 0.718 (0.414-1.248), and 0.443 (0.237-0.829), and HRs (95% CIs) for PFS were 0.706 (0.490-1.016), 0.709 (0.540-0.933), 0.711 (0.527-0.960), 0.501 (0.293-0.854), and 0.395 (0.214-0.727), respectively. In patients with 1, 2, 3, or ≥4 target tumor sites, HRs (95% CIs) for OS with avelumab + axitinib versus sunitinib were 0.912 (0.640-1.299), 0.715 (0.507-1.006), 0.679 (0.442-1.044), and 0.747 (0.346-1.615), and HRs (95% CIs) for PFS were 0.706 (0.548-0.911), 0.552 (0.422-0.723), 0.856 (0.589-1.244), and 0.662 (0.329-1.332), respectively. Across all subgroups, analyses of objective response rate and complete response rate favored avelumab + axitinib versus sunitinib, and a greater proportion of patients treated with avelumab + axitinib had tumor shrinkage. CONCLUSIONS: In post hoc analyses, first-line treatment with avelumab + axitinib was generally associated with efficacy benefits versus treatment with sunitinib in patients with advanced renal cell carcinoma across subgroups defined by different numbers of IMDC risk factors or target tumor sites.

A phase II open-label trial of avelumab plus axitinib in previously treated non-small-cell lung cancer or treatment-naïve, cisplatin-ineligible urothelial cancer.

BACKGROUND: We hypothesized that avelumab plus axitinib could improve clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC) or urothelial carcinoma (UC). PATIENTS AND METHODS: We enrolled previously treated patients with advanced or metastatic NSCLC, or untreated, cisplatin-ineligible patients with advanced or metastatic UC. Patients received avelumab 800 mg every 2 weeks (Q2W) and axitinib 5 mg orally two times daily. The primary endpoint was objective response rate (ORR). Immunohistochemistry was used to assess programmed death-ligand 1 (PD-L1) expression (SP263 assay) and the presence of CD8+ T cells (clone C8/144B). Tumor mutational burden (TMB) was assessed by whole-exome sequencing. RESULTS: A total of 61 patients were enrolled and treated (NSCLC, n = 41; UC, n = 20); 5 remained on treatment at data cut-off (26 February 2021). The confirmed ORR was 31.7% in the NSCLC cohort and 10.0% in the UC cohort (all partial responses). Antitumor activity was observed irrespective of PD-L1 expression. In exploratory subgroups, ORRs were higher in patients with higher (≥median) CD8+ T cells in the tumor. ORRs were higher in patients with lower TMB (

COVID-19 and pregnancy: clinical outcomes and scientific evidence about vaccination.

Pregnant women and their infants are at high risk to develop a severe COVID-19, with increased rates of hospitalisation to intensive care units, need for mechanical ventilation and mortality. Preterm birth, fetal vascular malperfusion, and premature rupture of membrane have been the most reported adverse pregnancy outcomes and these effects have been especially associated with the onset of the disease at early gestational age. The early expression of ACE2 and TMPRSS2 in human embryos has been proven, determining an increased susceptibility to SARS-CoV-2. Preterm infants born to women infected by SARS-CoV-2 have a higher risk of need for specialist neonatal care with prolonged hospitalization. Moreover, inflammation of developing embryos could cause long-term defects, regardless of vertical transmission of SARS-CoV-2. Due to Maternal Immune Activation (MIA), in utero inflammation is associated with neurodevelopmental, cognitive and psychiatric disorders in affected offspring. Despite risks that COVID-19 could induce in pregnancy, there are not many published data describing the safety and/or efficacy of COVID-19 vaccines in pregnant women, commonly not included in vaccine research. The evidence from the few pregnant women unintentionally enrolled in clinical trials and vaccinated suggests that COVID-19 vaccines, both based on mRNA and viral vectors, do not pose significant risks to the fetus or breastfeeding infants. Moreover, human studies using mRNA-based vaccines against Zika virus, influenza, and rabies have reported good safety and immunogenicity during pregnancy. In this review, we evaluate the role of COVID-19 in adverse pregnancy and neonatal outcomes and the need to vaccinate pregnant women.

Association of C-reactive protein with efficacy of avelumab plus axitinib in advanced renal cell carcinoma: long-term follow-up results from JAVELIN Renal 101.

BACKGROUND: C-reactive protein (CRP) is an important prognostic and predictive factor in advanced renal cell carcinoma (aRCC). We report the association of CRP levels at baseline and early after treatment with efficacy of avelumab plus axitinib or sunitinib from the phase III JAVELIN Renal 101 trial. PATIENTS AND METHODS: Patients were categorized into normal (baseline CRP <10 mg/l), normalized (baseline CRP ≥10 mg/l and ≥1 CRP value decreased to <10 mg/l during 6-week treatment), and non-normalized (CRP ≥10 mg/l at baseline and during 6-week treatment) CRP groups. Progression-free survival and best overall response from the second interim analysis and overall survival (OS) from the third interim analysis were assessed. RESULTS: In the avelumab plus axitinib and sunitinib arms, respectively, 234, 51, and 108 patients and 232, 36, and 128 patients were categorized into normal, normalized, and non-normalized CRP groups. In respective CRP groups, objective response rates [95% confidence interval (CI)] were 56.0% (49.4% to 62.4%), 66.7% (52.1% to 79.2%), and 45.4% (35.8% to 55.2%) with avelumab plus axitinib and 30.6% (24.7% to 37.0%), 41.7% (25.5% to 59.2%), and 19.5% (13.1% to 27.5%) with sunitinib; complete response rates were 3.8%, 11.8%, and 0.9% and 3.0%, 0%, and 1.6%, respectively. Median progression-free survival (95% CI) was 15.2 months (12.5-21.0 months), not reached (NR) [11.1 months-not estimable (NE)], and 7.0 months (5.6-9.9 months) with avelumab plus axitinib and 11.2 months (8.4-13.9 months), 11.2 months (6.7-13.8 months), and 4.2 months (2.8-5.6 months) with sunitinib; median OS (95% CI) was NR (42.2 months-NE), NR (30.4 months-NE), and 23.0 months (18.4-33.1 months) and NR (39.0 months-NE), 39.8 months (21.7-NE), and 19.1 months (16.3-25.3 months), respectively. Multivariate analyses demonstrated that normalized or non-normalized CRP levels were independent factors for the prediction of objective response rate or OS, respectively, with avelumab plus axitinib. CONCLUSIONS: In patients with aRCC, CRP levels at baseline and early after treatment may predict efficacy with avelumab plus axitinib.

Efficacy and correlative analyses of avelumab plus axitinib versus sunitinib in sarcomatoid renal cell carcinoma: post hoc analysis of a randomized clinical trial.

BACKGROUND: Among patients with advanced renal cell carcinoma (RCC), those with sarcomatoid histology (sRCC) have the poorest prognosis. This analysis assessed the efficacy of avelumab plus axitinib versus sunitinib in patients with treatment-naive advanced sRCC. METHODS: The randomized, open-label, multicenter, phase III JAVELIN Renal 101 trial (NCT02684006) enrolled patients with treatment-naive advanced RCC. Patients were randomized 1 : 1 to receive either avelumab plus axitinib or sunitinib following standard doses and schedules. Assessments in this post hoc analysis of patients with sRCC included efficacy (including progression-free survival) and biomarker analyses. RESULTS: A total of 108 patients had sarcomatoid histology and were included in this post hoc analysis; 47 patients in the avelumab plus axitinib arm and 61 in the sunitinib arm. Patients in the avelumab plus axitinib arm had improved progression-free survival [stratified hazard ratio, 0.57 (95% confidence interval, 0.325-1.003)] and a higher objective response rate (46.8% versus 21.3%; complete response in 4.3% versus 0%) versus those in the sunitinib arm. Correlative gene expression analyses of patients with sRCC showed enrichment of gene pathway scores for cancer-associated fibroblasts and regulatory T cells, CD274 and CD8A expression, and tumors with The Cancer Genome Atlas m3 classification. CONCLUSIONS: In this subgroup analysis of JAVELIN Renal 101, patients with sRCC in the avelumab plus axitinib arm had improved efficacy outcomes versus those in the sunitinib arm. Correlative analyses provide insight into this subtype of RCC and suggest that avelumab plus axitinib may increase the chance of overcoming the aggressive features of sRCC.

Elastic scattering and reaction mechanisms of the halo nucleus 11Be around the Coulomb barrier.

Collisions induced by (9,10,11)Be on a 64Zn target at the same c.m. energy were studied. For the first time, strong effects of the 11Be halo structure on elastic-scattering and reaction mechanisms at energies near the Coulomb barrier are evidenced experimentally. The elastic-scattering cross section of the 11Be halo nucleus shows unusual behavior in the Coulomb-nuclear interference peak angular region. The extracted total-reaction cross section for the 11Be collision is more than double the ones measured in the collisions induced by (9,10)Be. It is shown that such a strong enhancement of the total-reaction cross section with 11Be is due to transfer and breakup processes.

BMI influences CD20 kinetics in multiple sclerosis patients treated with ocrelizumab.

OBJECTIVES: Ocrelizumab (OCR) is a humanized monoclonal antibody targeting CD20 antigen exposed on B cells surface. Kinetic of B-cells repopulation after depletion therapy shows high intra and inter-individual variability. The aim of this study was to explore the influence of Body Mass Index (BMI) on kinetic of B-cell repopulation after treatment with OCR and on treatment response. METHODS: 108 Multiple Sclerosis (MS) patients were enrolled at the time of the first dose of OCR administration and prospectively evaluated. Clinical, instrumental activity and disability progression were analyzed. According to B cells count, patients were divided into two groups: with fast (FR) and with slow (SR) repopulation rate, respectively. RESULTS: Significant reduction of disease activity was observed in all patients and a stabilization of disease was obtained in progressive patients. Patients with FR had higher BMI compared to patients with a SR (p<0.001). Contrariwise no correlation between repopulation rate and treatment effectiveness was disclosed. CONCLUSIONS: In a real world setting we confirmed the effectiveness of OCR in relapsing remitting and progressive patients; patients with higher BMI had a FR. This suggests considering BMI for administration schedule although further investigations with longer follow up could improve treatment protocol and patient selection.