ABSTRACT
The ICARUS collaboration employed the 760-ton T600 detector in a successful 3-year physics run at the underground LNGS laboratory, performing a sensitive search for LSND-like anomalous νe appearance in the CERN Neutrino to Gran Sasso beam, which contributed to the constraints on the allowed neutrino oscillation parameters to a narrow region around 1 eV2. After a significant overhaul at CERN, the T600 detector has been installed at Fermilab. In 2020 the cryogenic commissioning began with detector cool down, liquid argon filling and recirculation. ICARUS then started its operations collecting the first neutrino events from the booster neutrino beam (BNB) and the Neutrinos at the Main Injector (NuMI) beam off-axis, which were used to test the ICARUS event selection, reconstruction and analysis algorithms. ICARUS successfully completed its commissioning phase in June 2022. The first goal of the ICARUS data taking will be a study to either confirm or refute the claim by Neutrino-4 short-baseline reactor experiment. ICARUS will also perform measurement of neutrino cross sections with the NuMI beam and several Beyond Standard Model searches. After the first year of operations, ICARUS will search for evidence of sterile neutrinos jointly with the Short-Baseline Near Detector, within the Short-Baseline Neutrino program. In this paper, the main activities carried out during the overhauling and installation phases are highlighted. Preliminary technical results from the ICARUS commissioning data with the BNB and NuMI beams are presented both in terms of performance of all ICARUS subsystems and of capability to select and reconstruct neutrino events.
ABSTRACT
BACKGROUND: Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy. METHODS: In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore. RESULTS: A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified. CONCLUSIONS: In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Papillomavirus Infections , Fibrosis , Humans , Immune Checkpoint Inhibitors , RNA, Messenger , Retrospective Studies , Vascular Endothelial Growth Factor AABSTRACT
PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Brain Neoplasms/drug therapy , Carmustine/therapeutic use , Glioblastoma/drug therapy , Neoplasm Recurrence, Local/drug therapy , AC133 Antigen/genetics , AC133 Antigen/metabolism , Adult , Aged , Angiogenesis Inhibitors/adverse effects , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Bevacizumab/adverse effects , Brain Neoplasms/blood supply , Brain Neoplasms/genetics , Brain Neoplasms/mortality , Carmustine/adverse effects , Chitinase-3-Like Protein 1/genetics , Colombia , DNA Modification Methylases/metabolism , DNA Repair Enzymes/metabolism , Drug Administration Schedule , Female , Genes, erbB-1 , Genes, p53 , Glioblastoma/blood supply , Glioblastoma/genetics , Glioblastoma/mortality , Humans , Isocitrate Dehydrogenase/genetics , Male , Methylation , Middle Aged , Mutation , Neoplasm Recurrence, Local/blood supply , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/mortality , Progression-Free Survival , RNA, Messenger/metabolism , Receptors, Platelet-Derived Growth Factor/genetics , Survival Analysis , Tumor Suppressor Proteins/metabolism , Young AdultABSTRACT
BACKGROUND: The procedure of radical peritonectomy followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is considered the standard treatment for peritoneal cancers. AIMS: To evaluate various outcomes in a cohort of patients with peritoneal tumors treated with HIPEC. METHODS: Twenty-four patients consecutively treated with radical peritonectomy plus HIPEC within the time frame of November 2007 to July 2010 were enrolled; 15 (62%) had tumors of appendicular origin, 4 (16.7%) had primary peritoneal tumors, 2 had ovarian carcinomas and there was one case of colon cancer, one carcinosarcoma and one hemangioendothelioma. Mean age was 53 years (range: 26-68) and median follow-up was 14.2 months (range: 1-32). Demographic data, histology, peritoneal cancer index (PCI), surgical procedure characteristics, recurrence-free survival (RFS), and overall survival (OS) were all evaluated. Short-term morbidity and mortality were also determined. RESULTS: Complete cytoreduction was achieved in 18 patients (75%). Mean PCI was 15 (<10: 41% and >10: 58%), and the median (range) for surgery duration, length of stay in the Intensive Care Unit, parenteral nutritional support, and hospital stay were 12,5 (7-20) hours, 11,4 (2-74) days, 13,8 (12-65) days, and 29,1 (10-90) days, respectively. One patient (4%) died 6 months after the procedure, due to multiple associated complications. Considerable morbidity was seen in 52% of cases, including thromboembolic events (41%), catheter-related bacteremia (29%), fistulas (29%), and nephrotoxicity (25%). Six patients (25%) recurred after a median of 21 months of RFS. CONCLUSIONS: Cytoreductive surgery plus HIPEC in well-selected patients presenting with tumors that affect the peritoneum is a procedure that can be carried out in Colombia with an adequate safety and effectiveness profile. Mortality was similar to that reported in the international literature.
Subject(s)
Antineoplastic Agents/therapeutic use , Hyperthermia, Induced , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Adult , Combined Modality Therapy , Female , Hospitals, Teaching , Humans , Length of Stay , Male , Peritoneal Neoplasms/mortality , Survival Analysis , Treatment OutcomeABSTRACT
Se presenta el caso de un paciente con recesión gingival en un incisivo inferior, tratado con un injerto de tejido conectivo obtenido del paladar, la técnica utilizada para la toma se vale de una incisión única que permite una cicatrización por primera intención y mínimas molestias postoperatorias. El cubrimiento de la recesión en el presente caso clínico fue total (AU)
Subject(s)
Humans , Male , Adolescent , Gingival Recession/surgery , Connective Tissue , Surgical Flaps , Periodontal Index , Periodontal Pocket/diagnosis , Toothbrushing/methods , Dental Scaling/methods , Gingiva/surgeryABSTRACT
Se presenta el caso de un paciente con recesión gingival en un incisivo inferior, tratado con un injerto de tejido conectivo obtenido del paladar, la técnica utilizada para la toma se vale de una incisión única que permite una cicatrización por primera intención y mínimas molestias postoperatorias. El cubrimiento de la recesión en el presente caso clínico fue total