Moderately Escalated Hypofractionated (Chemo) Radiotherapy Delivered with Helical Intensity-Modulated Technique in Stage III Unresectable Non-Small Cell Lung Cancer

Purpose: To assess clinical outcomes and toxicities in patients with stage III unresectable non-small cell lung cancer (NSCLC) treated with a moderately escalated hypofractionated radiotherapy delivered with Helical Intensity-Modulated Technique in combination with sequential or concurrent chemotherapy. Materials and Methods: Sixty-one consecutive patients considered non-progressive after two cycles of induction chemotherapy were treated with a moderately escalated hypofractionated radiation course of 30 daily fractions of 2.25–2.28 Gy each administered in 6 weeks up to a total dose of 67.5–68.4 Gy (range, 64.5–71.3 Gy). Thirty-two received sequential RT after two more cycles (total = 4 cycles) of chemotherapy, while 29 were treated with concurrent chemo-radiation. The target was considered the gross tumor volume and the clinically proven nodal regions, without elective nodal irradiation. Results: With a median follow up of 27 months (range 6–40), 1-year and 2-year OS rate for all patients was 77 and 53%, respectively, with a median survival duration of 18.6 months in the sequential group and 24.1 months in the concomitant group. No Grade ≥4 acute and late toxicity was reported. Acute Grade 3 treatment-related pneumonitis was detected in 10% of patients. Two patients, both receiving the concurrent schedule, developed a Grade 3 acute esophagitis. The overall incidence of late Grade 3 lung toxicity was 5%. No patients experienced a Grade 3 late esophageal toxicity. Conclusion: A moderately hypofractionated radiation course delivered with a Helical Intensity-Modulated Technique is a feasible treatment option for patients with unresectable locally advanced NSCLC receiving chemotherapy (sequentially or concurrently). Hypofractionated radiotherapy with a dedicated technique allows safely dose escalation, minimizing the effect of tumor repopulation that may occur with prolonged treatment time

A phase II study on the role of gemcitabine plus romidepsin (GEMRO regimen) in the treatment of relapsed/refractory peripheral T-cell lymphoma patients

Background: There is no consensus regarding optimal treatment for peripheral T-cell lymphomas (PTCL), especially in relapsed or refractory cases, which have very poor prognosis and a dismal outcome, with 5-year overall survival of 30 %. Methods: A multicenter prospective phase II trial was conducted to investigate the role of the combination of gemcitabine plus romidepsin (GEMRO regimen) in relapsed/refractory PTCL, looking for a potential synergistic effect of the two drugs. GEMRO regimen contemplates an induction with romidepsin plus gemcitabine for six 28-day cycles followed by maintenance with romidepsin for patients in at least partial remission. The primary endpoint was the overall response rate (ORR); secondary endpoints were survival, duration of response, and safety of the regimen. Results: The ORR was 30 % (6/20) with 15 % (3) complete response (CR) rate. Two-year overall survival was 50 % and progression-free survival 11.2 %. Grade >= 3 adverse events were represented by thrombocytopenia (60 %), neutropenia (50 %), and anemia (20 %). Two patients are still in CR with median response duration of 18 months. The majority of non-hematological toxicities were mild and transient. No treatment-related death occurred and no toxicity led to treatment interruption. Conclusions: GEMRO combination regimen shows efficacy data similar to those of single-agent romidepsin with additional hematologic toxicities. Synergy observed in preclinical phase did not turn into ability to improve clinical outcomes

The Italian open data meteorological portal: MISTRAL

AbstractAt the national level, in Italy, observational and forecast data are collected by various public bodies and are often kept in various small, heterogeneous and non‐interoperable repositories, released under different licenses, thus limiting the usability for external users. In this context, MISTRAL (the Meteo Italian SupercompuTing PoRtAL) was launched as the first Italian meteorological open data portal, with the aim of promoting the reuse of meteorological data sets available at national level coverage. The MISTRAL portal provides (and archives) meteorological data from various observation networks, both public and private, and forecast data that are generated and post‐processed within the Consortium for Small‐scale Modeling‐Limited Area Model Italia (COSMO‐LAMI) agreement using high performance computing (HPC) facilities. Also incorporated is the Italy Flash Flood use case, implemented with the collaboration of European Centre for Medium‐Range Weather Forecasts (ECMWF), which exploits cutting edge advances in HPC‐based post‐processing of ensemble precipitation forecasts, for different model resolutions, and applies those to deliver novel blended‐resolution forecasts specifically for Italy. Finally, in addition to providing architectures for the acquisition and display of observational data, MISTRAL also delivers an interactive system for visualizing forecast data of different resolutions as superimposed multi‐layer maps

Surgical Antimicrobial Prophylaxis in Patients of Neonatal and Pediatric Age Undergoing Orthopedic and Hand Surgery: A RAND/UCLA Appropriateness Method Consensus Study

Surgical site infections (SSIs) represent a potential complication in any type of surgery and can occur up to one year after the procedure in the case of implant placement. In the field of orthopedic and hand surgery, the rate of SSIs is a relevant issue, considering the need for the placement of synthesis devices and the type of some interventions (e.g., exposed fractures). This work aims to provide guidance on the management of peri-operative antibiotic prophylaxis for the pediatric and neonatal population undergoing orthopedic and hand surgery in order to standardize the management of patients and to reduce, on the one hand, the risk of SSI and, on the other, the development of antimicrobial resistance. The following scenarios were considered: (1) bloodless fracture reduction; (2) reduction of unexposed fracture and grade I and II exposed fracture; (3) reduction of grade III exposed fracture or traumatic amputation; (4) cruel fracture reduction with percutaneous synthesis; (5) non-traumatic amputation; (6) emergency intact skin trauma surgery and elective surgery without synthetic media placement; (7) elective orthopedic surgery with prosthetic and/or synthetic media placement and spinal surgery; (8) clean elective hand surgery with and without bone involvement, without use of synthetic means; (9) surgery of the hand on an elective basis with bone involvement and/or with use of synthetic means. This manuscript has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies and represents, in our opinion, the most complete and up-to-date collection of recommendations regarding the behavior to be adopted in the peri-operative setting in neonatal and pediatric orthopedic and hand surgery. The specific scenarios developed are aimed at guiding the healthcare professional in practice to ensure the better and standardized management of neonatal and pediatric patients, together with an easy consultation

Surgical Antimicrobial Prophylaxis in Neonates and Children Undergoing Neurosurgery: A RAND/UCLA Appropriateness Method Consensus Study

Pediatric neurosurgery is a highly specialized branch of surgery in which surgical site infections (SSIs) are potentially serious complications that can also adversely affect a good surgical outcome, compromising functional recovery and, in some cases, even putting the patient's life at risk. The main aim of this consensus document is to provide clinicians with a series of recommendations on antimicrobial prophylaxis for neonates and children undergoing neurosurgery. The following scenarios were considered: (1) craniotomy or cranial/cranio-facial approach to craniosynostosis; (2) neurosurgery with a trans-nasal-trans-sphenoidal approach; (3) non-penetrating head injuries; (4) penetrating head fracture; (5) spinal surgery (extradural and intradural); (6) shunt surgery or neuroendoscopy; (7) neuroendovascular procedures. Patients undergoing neurosurgery often undergo peri-operative antibiotic prophylaxis, with different schedules, not always supported by scientific evidence. This consensus provides clear and shared indications, based on the most updated literature. This work has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies, and represents, in our opinion, the most complete and up-to-date collection of recommendations on the behavior to be held in the peri-operative setting in this type of intervention, in order to guide physicians in the management of the patient, standardize approaches and avoid abuse and misuse of antibiotics

Peri-Operative Prophylaxis in Patients of Neonatal and Pediatric Age Subjected to Cardiac and Thoracic Surgery: A RAND/UCLA Appropriateness Method Consensus Study

Surgical site infections (SSIs) represent a potential complication of surgical procedures, with a significant impact on mortality, morbidity, and healthcare costs. Patients undergoing cardiac surgery and thoracic surgery are often considered patients at high risk of developing SSIs. This consensus document aims to provide information on the management of peri-operative antibiotic prophylaxis for the pediatric and neonatal population undergoing cardiac and non-cardiac thoracic surgery. The following scenarios were considered: (1) cardiac surgery for the correction of congenital heart disease and/or valve surgery; (2) cardiac catheterization without the placement of prosthetic material; (3) cardiac catheterization with the placement of prosthetic material; (4) implantable cardiac defibrillator or epicardial pacemaker placement; (5) patients undergoing ExtraCorporal Membrane Oxygenation; (6) cardiac tumors and heart transplantation; (7) non-cardiac thoracic surgery with thoracotomy; (8) non-cardiac thoracic surgery using video-assisted thoracoscopy; (9) elective chest drain placement in the pediatric patient; (10) elective chest drain placement in the newborn; (11) thoracic drain placement in the trauma setting. This consensus provides clear and shared indications, representing the most complete and up-to-date collection of practice recommendations in pediatric cardiac and thoracic surgery, in order to guide physicians in the management of the patient, standardizing approaches and avoiding the abuse and misuse of antibiotics

Diagnosis of Imported Dengue and Zika Virus Infections in Italy from November 2015 to November 2022: Laboratory Surveillance Data from a National Reference Laboratory

Dengue (DENV) and Zika (ZIKV) viruses are mosquito-borne human pathogens. In Italy, the presence of the competent vector Aedes albopictus increases the risk of autochthonous transmission, and a national plan for arboviruses prevention, surveillance, and response (PNA 2020–2025) is in place. The results of laboratory diagnosis of both viruses by the National Reference Laboratory for arboviruses (NRLA) from November 2015 to November 2022 are presented. Samples from 655 suspected cases were tested by both molecular and serological assays. Virus and antibody kinetics, cross-reactivity, and diagnostic performance of IgM ELISA systems were analysed. Of 524 cases tested for DENV, 146 were classified as confirmed, 7 as probable, while 371 were excluded. Of 619 cases tested for ZIKV, 44 were classified as confirmed, while 492 were excluded. All cases were imported. Overall, 75.3% (110/146) of DENV and 50% (22/44) of ZIKV cases were confirmed through direct virus detection methods. High percentages of cross reactivity were observed between the two viruses. The median lag time from symptoms onset to sample collection was 7 days for both DENV molecular (range 0–20) and NS1 ELISA (range 0–48) tests, with high percentages of positivity also after 7 days (39% and 67%, respectively). For ZIKV, the median lag time was 5 days (range 0–22), with 16% positivity after 7 days. Diagnostic performance was assessed with negative predictive values ranging from 92% to 95% for the anti-DENV systems, and of 97% for the ZIKV one. Lower positive predictive values were seen in the tested population (DENV: 55% to 91%, ZIKV: 50%). DENV and ZIKV diagnosis by molecular test is the gold standard, but sample collection time is a limitation. Serological tests, including Plaque Reduction Neutralization Test, are thus necessary. Co-circulation and cross-reactivity between the two viruses increase diagnostic difficulty. Continuous evaluation of diagnostic strategies is essential to improve laboratory testing

Cure indicators and prevalence by stage at diagnosis for breast and colorectal cancer patients: A population‐based study in Italy

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5-year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III-IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but <= 1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III-IV. TTC was <= 10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow-up in the years after diagnosis, thus avoiding patients' discrimination

The eEF1γ Subunit Contacts RNA Polymerase II and Binds Vimentin Promoter Region

Here, we show that the eukaryotic translation elongation factor 1 gamma (eEF1γ) physically interacts with the RNA polymerase II (pol II) core subunit 3 (RPB3), both in isolation and in the context of the holo-enzyme. Importantly, eEF1γ has been recently shown to bind Vimentin mRNA. By chromatin immunoprecipitation experiments, we demonstrate, for the first time, that eEF1γ is also physically present on the genomic locus corresponding to the promoter region of human Vimentin gene. The eEF1γ depletion causes the Vimentin protein to be incorrectly compartmentalised and to severely compromise cellular shape and mitochondria localisation. We demonstrate that eEF1γ partially colocalises with the mitochondrial marker Tom20 and that eEF1γ depletion increases mitochondrial superoxide generation as well as the total levels of carbonylated proteins. Finally, we hypothesise that eEF1γ, in addition to its role in translation elongation complex, is involved in regulating Vimentin gene by contacting both pol II and the Vimentin promoter region and then shuttling/nursing the Vimentin mRNA from its gene locus to its appropriate cellular compartment for translation

Pre-Existing T- and B-Cell Defects in One Progressive Multifocal Leukoencephalopathy Patient

Progressive multifocal leukoencephalopathy (PML) usually occurs in patients with severe immunosuppression, hematological malignancies, chronic inflammatory conditions or receiving organ transplant. Recently, PML has also been observed in patients treated with monoclonal antibodies. By taking advantage of the availability of samples from a multiple sclerosis (MS) patient treated with natalizumab, the antibody anti-α4 integrin, who developed PML and was monitored starting before therapy initiation, we investigated the fate of T and B lymphocytes in the onset of PML. Real-time PCR was used to measure new T- and B-cell production by means of T-cell receptor excision circle (TREC) and K-deleting recombination excision circle (KREC) analysis and to quantify transcripts for CD34, terminal-deoxynucleotidyltransferase, and V pre-B lymphocyte gene 1. T- and B-cell subsets and T-cell heterogeneity were measured by flow cytometry and spectratyping. The data were compared to those of untreated and natalizumab-treated MS patients and healthy donors. Before therapy, a patient who developed PML had a low TREC and KREC number; TRECs remained low, while KRECs and pre-B lymphocyte gene 1 transcripts peaked at 6 months of therapy and then decreased at PML diagnosis. Flow cytometry confirmed the deficient number of newly produced T lymphocytes, counterbalanced by an increase in TEMRA cells. The percentage of naive B cells increased by approximately 70% after 6 months of therapy, but B lymphocyte number remained low for the entire treatment period. T-cell heterogeneity and immunoglobulins were reduced