Clinical benefit of adding oxaliplatin to standard neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a meta-analysis : Oxaliplatin in neoadjuvant treatment for rectal cancer

Abstract. Background: To evaluate the treatment tolerance and clinical outcomes in patients aged 70 years and older with locally advanced oropharyngeal cancer treated by definitive intensity-modulated radiation therapy (IMRT). Patients and Methods: We retrospectively analyzed 15 consecutive elderly patients, with histologically-proven squamous cell carcinoma of the oropharynx, staged T3-4 with or without involved lymph nodes at diagnosis, who received definitive sequential IMRT (70 Gy; 2 Gy/fraction). Adult Comorbidity Evaluation-27 (ACE-27) score was calculated and its influence on treatment tolerance and clinical outcomes was analyzed. Results: A total of 15 patients were included with a median age of 77 years (range=70-88 years). At baseline, 8 patients (53.3%) had an ACE-27 score of 1, and the remainder (n=7, 46.7%) had a comorbidity index of 0. All patients completed programmed IMRT treatment, without any reduction of total dose. Oral pain and mucositis were the most common acute side-effects, classified as grade 3 in 6 patients (40%) only. Xerostomia was reported in 13 patients (86.7%), without severe manifestation. There was no hematological toxicity. ACE-27 score was not related to higher severe acute toxicity. No patients experienced grade 3 or more late toxicity. Five-year overall survival and disease-free survival rates were 63.6% (95% confidence interval=32.7-83.3%) and 55% (95% confidence interval=24.4-77.6%), respectively. Comorbidity score did not influence survival outcomes, both overall survival (p=0.46) and disease-free survival (p=0.55). Conclusion: Treatment tolerance, as well as survival outcomes were good in elderly oropharyngeal cancer patients treated with definitive sequential IMRT. Due to age and comorbidity, no dose or volume reduction for IMRT should be considered in this setting of patients. A prospective randomized trial with a large sample size should be conducted to confirm our result

Small fragments sodium sulfated hyaluronate, more than hyaluronic acid, reduces LPS-induced cytokine/chemokine levels in HaCaT cells

Hyaluronic acid (HA) is a linear non-sulphated glycosaminoglycan, used in dermatology as a biomaterial for bioengineering purposes, temporary dermal filler, stimulation of wound healing as well as drug vehicle in topical formulations. In addition to the well-characterized structural properties, extensive research on HA has revealed a range of vastly immunemodulatory effects, dependent on its size. In this in vitro study we investigated the ability of HA-S3, a small fragment HA (MW, molecular weight: 68 kDa) with degree of sulphatation of 3 and of HA fraction (MW:210 kDa) to reduce the bacterial induced inflammatory response in spontaneous immortalized keratinocytes. To this purpose, HaCaT cells were treated for 24 hours with 25 µg/ml of E. Coli derived bacterial lipopolysaccharide (LPS) in absence or presence of small fragment HA-S3 or HA. Cell viability was thereafter assessed using trypan blue stain and interleukin (IL)-8, IL-1β and tumor necrosis factor alpha (TNF-α) concentrations were determined in cell supernatants by single enzyme-linked immunoadsorbent assay (ELISA). Our results showed that cell viability was not affected either by HA-S3 or HA which in turn were able to reduce LPS-induced mortality. HA and especially HA-S3 were able to significantly reduce LPS-induced pro-inflammatory cytokines. Our observation might suggest new perspectives in the development of HA-S3 containing topical products able to modulate cutaneous inflammatory response

Characteristics of people living in Italy after a cancer diagnosis in 2010 and projections to 2020

BACKGROUND: Estimates of cancer prevalence are widely based on limited duration, often including patients living after a cancer diagnosis made in the previous 5 years and less frequently on complete prevalence (i.e., including all patients regardless of the time elapsed since diagnosis). This study aims to provide estimates of complete cancer prevalence in Italy by sex, age, and time since diagnosis for all cancers combined, and for selected cancer types. Projections were made up to 2020, overall and by time since diagnosis. METHODS: Data were from 27 Italian population-based cancer registries, covering 32% of the Italian population, able to provide at least 7 years of registration as of December 2009 and follow-up of vital status as of December 2013. The data were used to compute the limited-duration prevalence, in order to estimate the complete prevalence by means of the COMPREV software. RESULTS: In 2010, 2,637,975 persons were estimated to live in Italy after a cancer diagnosis, 1.2 million men and 1.4 million women, or 4.6% of the Italian population. A quarter of male prevalent cases had prostate cancer (n\u2009=\u2009305,044), while 42% of prevalent women had breast cancer (n\u2009=\u2009604,841). More than 1.5 million people (2.7% of Italians) were alive since 5 or more years after diagnosis and 20% since 6515 years. It is projected that, in 2020 in Italy, there will be 3.6 million prevalent cancer cases (+\u200937% vs 2010). The largest 10-year increases are foreseen for prostate (+\u200985%) and for thyroid cancers (+\u200979%), and for long-term survivors diagnosed since 20 or more years (+\u200945%). Among the population aged 6575 years, 22% will have had a previous cancer diagnosis. CONCLUSIONS: The number of persons living after a cancer diagnosis is estimated to rise of approximately 3% per year in Italy. The availability of detailed estimates and projections of the complete prevalence are intended to help the implementation of guidelines aimed to enhance the long-term follow-up of cancer survivors and to contribute their rehabilitation need

Differential expression of type I interferon and inflammatory genes in SARS-CoV-2-infected patients treated with monoclonal antibodies

Introduction: Considering the reported efficacy of monoclonal antibodies (mAbs) directed against the Spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in reducing disease severity, the aim of this study was to investigate the innate immune response before and after mAbs treatment in 72 vaccinated and 31 unvaccinated SARS-CoV-2 patients. Methods: The mRNA levels of IFN-I, IFN-related genes and cytokines were evaluated using RT/real-time quantitative PCR. Results: Vaccinated patients showed increased rate of negative SARS-CoV-2 PCR tests on nasopharyngeal swab compared with unvaccinated ones after mAbs treatment (p = .002). Unvaccinated patients had lower IFN-α/ω and higher IFN-related genes (IFNAR1, IFNAR2, IRF9, ISG15, ISG56 and IFI27) and cytokines (IL-6, IL-10 and TGF-β) mRNA levels compared to vaccinated individuals before mAbs (p < .05 for all genes). Increased IFN-α/ω, IFNAR1, IFNAR2 and IRF9 levels were observed in unvaccinated patients after mAbs treatment, while the mRNA expression ISGs and IL-10 were reduced in all patients. Conclusion: These data suggest that anti-S vaccinated patients have increased levels of innate immune genes compared to unvaccinated ones. Also, gene expression changes in IFN genes after mAbs administration are different according to the vaccination status of patients

Rationale and Design of the PARTHENOPE Trial: A Two-by-Two Factorial Comparison of Polymer-Free vs. Biodegradable-Polymer Drug-Eluting Stents and Personalized vs. Standard Duration of Dual Antiplatelet Therapy in All-Comers Undergoing PCI.

BACKGROUND Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 13 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the non-inferiority between stents with respect to a device-oriented composite endpoint of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI

Switching from VEDOlizumab intravenous to subcutaneous formulation in ulcerative colitis patients in clinical remission: The SVEDO Study, an IG-IBD study

Background: The administration of biological drugs in inflammatory bowel diseases (IBD) is increasingly moving from intravenous to subcutaneous formulations. Aims: To evaluate the efficacy and safety of vedolizumab subcutaneous administration after switching from intravenous administration in ulcerative colitis (UC) patients in corticosteroid-free clinical remission. Methods: An observational, multicentre, prospective study was conducted by the Italian Group for the study of IBD (IG-IBD). UC patients in clinical remission (pMAYO &lt; 2) not receiving steroids for &gt; 8 months before the switch, and with at least 6 months of follow-up were included. Switch from intravenous to subcutaneous vedolizumab was defined as successful in patients not experiencing a disease flare (pMAYO ≥ 2) or needing oral steroids or stopping subcutaneous vedolizumab during the 6 months of follow-up after the switch. Results: Overall, 168 patients were included. The switch was a success in 134 patients (79.8%). Vedolizumab retention rate was 88.7% at month six. C-reactive protein and faecal calprotectin values did not change after the switch (p = 0.07 and p = 0.28, respectively). Ten of the 19 patients who stopped subcutaneous formulation switched back to intravenous formulation recapturing clinical remission in 80%. Side effects were observed in 22 patients (13.1%). Conclusion: Effectiveness of switching from intravenous to subcutaneous vedolizumab formulation in UC patients in steroid-free clinical remission is confirmed in a real-world setting

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

The X-ray Polarization Probe mission concept

The X-ray Polarization Probe (XPP) is a second generation X-ray polarimeter following up on the Imaging X-ray Polarimetry Explorer (IXPE). The XPP will offer true broadband polarimetery over the wide 0.2-60 keV bandpass in addition to imaging polarimetry from 2-8 keV. The extended energy bandpass and improvements in sensitivity will enable the simultaneous measurement of the polarization of several emission components. These measurements will give qualitatively new information about how compact objects work, and will probe fundamental physics, i.e. strong-field quantum electrodynamics and strong gravity.Comment: submitted to Astrophysics Decadal Survey as a State of the Profession white pape