Explore the vast range of titles available.

Background Metastatic colorectal cancer (mCRC) remains an incurable disease with a poor prognosis. Recently, the global phase 3 SUNLIGHT study demonstrated that adding bevacizumab to trifluridine/tipiracil (FTD/TPI) in refractory disease significantly improves overall survival (OS). As a result, this combination is set to become the new standard of care for refractory mCRC. Immune checkpoint inhibitors (ICIs), including Pembrolizumab, have shown excellent results in mCRC patients with mismatch-repair deficiency (dMMR) or high microsatellite instability (MSI-H) mCRC. Additionally, recent trials evaluating both concomitant and sequential chemoimmunotherapy in mismatch-repair-proficient (pMMR) and microsatellite-stable (MSS) mCRC have yielded promising outcomes. Dendritic cell (DC) vaccines, though historically limited in effectiveness, show potential when combined with ICIs. Preliminary studies suggest they enhance chemotherapy response while maintaining favorable safety profiles. These evidences support the exploration of immunotherapy and FTD/TPI plus Bevacizumab in pMMR/MSS mCRC patients. Methods This is a single-arm, open-label, multicenter, phase 2 clinical trial evaluating the clinical and immunological activity of an innovative approach combining induction immunotherapy (Pembrolizumab plus DC vaccine) followed by maintenance chemotherapy (FTD/TPI plus Bevacizumab) in patients with refractory MSS/pMMR mCRC. The primary endpoint is the objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), safety, and overall survival (OS). Discussion This study explores a novel sequential immunochemotherapy approach combining a DC-based vaccine with anti-PD-1 immunotherapy and standard chemotherapy in patients with refractory pMMR/MSS mCRC. By integrating cellular immunotherapy without omitting the current standard of care (FTD/TPI plus bevacizumab), the trial aims to enhance treatment efficacy in a setting traditionally resistant to immunological strategies. To the best of our knowledge, this is the only ongoing trial investigating this therapeutic combination in this specific patient population. Trial registration This study, acronym CombiCoR-Vax, has been registered on clinicaltrials.gov registry with identifier NCT06522919, on July 9, 2024.

Together with Granulicatella spp., A. defectiva was formerly classified within the group of nutritionally variant streptococci (NVS). NVS-related endocarditis has been associated with higher rates of complications, bacteriological failure, and mortality compared to other streptococci, partially due to challenges related to timely and accurate identification. PJI caused by A. defectiva are rarely reported, and standardized management strategies have not yet been established. We describe a case of a 68-year-old man with concomitant A. defectiva PJI and native mitral valve endocarditis. The patient was managed conservatively for endocarditis and subsequently underwent a two-stage arthroplasty of the infected prosthetic knee. A. defectiva was identified using MALDI-TOF mass spectrometry on both synovial fluid and blood cultures. As penicillin susceptibility data were not available, the patient was treated with vancomycin at a dose of 2 g/day, resulting in a favorable clinical response. In addition, we performed a literature review on A. defectiva and Granulicatella PJI. Despite the limited number of reported cases in the literature, the findings suggest a potential correlation between clinical outcomes and antimicrobial treatment duration. Further comprehensive studies are needed to establish standardized management strategies for A. defectiva and Granulicatella PJI.

Glioblastoma (GBM) is a poor prognosis grade 4 glioma. After surgical resection, the standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Our previous data on melanoma patients showed that Dendritic Cell vaccination (DCvax) could increase the amount of intratumoral-activated cytotoxic T lymphocytes. This is a single-arm, monocentric, phase II trial in two steps according to Simon's design. The trial aims to evaluate progression-free survival (PFS) at three months and the safety of a DCvax integrated with standard therapy in resected GBM patients. DCvax administration begins after completion of RT-CTwith weekly administrations for 4 weeks, then is alternated monthly with TMZ cycles. The primary endpoints are PFS at three months and safety. One of the secondary objectives is to evaluate the immune response both and (DTH skin test). By December 2022, the first pre-planned step of the study was concluded with the enrollment, treatment and follow up of 9 evaluable patients. Two patients had progressed within three months after leukapheresis, but none had experienced DCvax-related G3-4 toxicities Five patients experienced a positive DTH test towards KLH and one of these also towards autologous tumor homogenate. The median PFS from leukapheresis was 11.3 months and 12.2 months from surgery. This combination therapy is well-tolerated, and the two endpoints required for the first step have been achieved. Therefore, the study will proceed to enroll the remaining 19 patients. (Eudract number: 2020-003755-15 https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-003755-15/IT).

The fecal immunochemical test (FIT) is widely implemented as a first-line tool in organized colorectal cancer (CRC) screening programs, including Italy. Following a positive FIT, colonoscopy is recommended. Computer-aided detection (CADe) systems have the potential to enhance adenoma detection, particularly in FIT-positive populations where identifying advanced adenomas is critical for cancer prevention. This study evaluated the diagnostic performance of CADe-assisted colonoscopy versus standard colonoscopy (SC) in a FIT-based screening cohort. In this multicenter, randomized controlled trial, patients with a positive FIT result were randomized to undergo either CADe-assisted or standard colonoscopy. The primary endpoint was the advanced adenoma detection rate (AADR). Secondary endpoints included overall adenoma detection rate (ADR), adenomas per colonoscopy (APC), and mean withdrawal time (WT). Of 1077 patients enrolled, 68 were excluded due to inadequate bowel preparation, leaving 1009 patients for analysis (CADe: n = 506; SC: n = 503). AADR was comparable between the groups (21.3% vs. 20.5%, p = 0.794). However, CADe significantly improved ADR (67.6% vs. 59.8%, p = 0.012) and APC (1.82 ± 2.12 vs. 1.34 ± 1.81, p < 0.001). Mean WT was longer in the CADe group (17.10 ± 8.28 min vs. 16.13 ± 8.28 min, p = 0.016). In a FIT-based organized CRC screening setting, CADe did not enhance detection of AADR with a modest increase in withdrawal time. NCT04441580.

Background The therapeutic role and prognostic relevance of lymphadenectomy in mast cell tumor (MCT) has historically been evaluated on regional rather than sentinel lymph nodes. Hypothesis/Objectives To update information about the association of histological nodal (HN) classes with clinical outcome in dogs with MCT after tumor excision and extirpation of normal‐sized sentinel nodes (SLN) guided by radiopharmaceutical. Animals Ninety‐four dogs with histologically‐confirmed treatment‐naïve MCT (71 cutaneous, 22 subcutaneous and 1 conjunctival MCT) were included if without: distant metastases, lymphadenomegaly, concurrent mixed cutaneous, and subcutaneous MCT. Methods This was a monoistitutional cohort study. Tumors characteristics were retrieved and SLNs were classified according to Weishaar's system. Incidence of MCT‐related events (local, nodal, distant relapse), de novo MCT or other tumors and death (MCT‐related and non‐MCT‐related), were recorded. Incidence curves were compared among the HN classes. Results Twenty‐seven dogs had HN0, 19 HN1, 37 HN2, and 11 HN3 SLN. Thirteen (2 HN0, 4 HN2, and 7 HN3) received adjuvant chemotherapies. Kiupel high grade, increasing number of SLN and lymphocentrums were associated with higher HN classes. Five dogs died for MCT‐related causes: 1 low‐grade (HN0) and 1 subcutaneous (HN3) had a local relapse, 2 high‐grade had distant relapse (HN3‐HN0) and 1 dog developed disease progression from a de novo subcutaneous MCT. No nodal relapse was registered. Fourteen dogs developed de novo MCTs. Conclusion/Discussion Low grade/low‐risk MCT with nonpalpable and normal sized SLN have a favorable outcome independently from the HN. Result should be considered strictly related to the successful SLN detection guided pre‐ and intraoperative by radiopharmaceutical markers.

Background No data regarding near-infrared fluorescence (NIRF) with indocyanine green and its comparison with lymphoscintigraphy are available for sentinel lymph node identification in canine and feline solid malignant tumors. This study compares both techniques in sentinel lymphocentrums mapping and surgical guided sentinel lymph node extirpation. Results Fifty-four animals with 60 tumors were included, and the combined use of lymphoscintigraphy and NIRF was applied: 80 sentinel lymphocentrums were surgically explored, and 113 sentinel lymph nodes were extirpated. This combination allowed the detection of at least one sentinel lymphocentrum and sentinel lymph node per each tumor. During mapping, the sentinel lymphocentrum detection rate with NIRF was 93%, similar to lymphoscintigraphy with a handheld intraoperative gamma probe (92%). No significant differences among techniques were observed in the surgical guided exploration phase, except that the number of fluorescent sentinel lymph nodes was significantly higher than radioactive ones, and the number of detected metastatic lymph nodes was comparable among the techniques. Surgeons subjectively considered the intraoperative gamma probe more helpful in 46.5% of sentinel lymph node extirpations, NIRF more helpful in 24.2%, and both techniques equally helpful in 29.3% of cases. Overall, they deemed the use of intraoperative gamma probe superior to NIRF for axillary lymphadenectomies and NIRF superior to lymphoscintigraphy for head and neck lymphadenectomies. Conclusions Despite some differences between the techniques, NIRF with indocyanine green can be considered a practical and viable alternative to lymphoscintigraphy for sentinel lymphocentrum mapping and guided sentinel lymph node removal in small animal oncologic practice, particularly where lymphoscintigraphy is not accessible.

The long-standing claim of dark matter detection by the DAMA experiment remains a crucial open question in astroparticle physics. A key step towards its independent verification is the development of NaI(Tl)-based detectors with improved sensitivity at low energies. The majority of NaI(Tl)-based experiments rely on conventional photomultiplier tubes (PMTs) as single photon detectors, which present technological limitations in terms of light collection, intrinsic radioactivity and high noise contribution at keV energies. ASTAROTH is an R&D project developing a NaI(Tl)-based detector where the scintillation light is read out by silicon photomultipliers (SiPMs) matrices. SiPMs exhibit high photon detection efficiency, negligible radioactivity, and, most importantly, a dark noise nearly two orders of magnitude lower than PMTs, when operated at cryogenic temperature. To this end, ASTAROTH features a custom-designed cryostat based on a bath of cryogenic fluid, able to safely operate the detector and the read-out electronics down to about 80 K. This work reports the first experimental characterization of an approximately 360 g NaI(Tl) detector read out by a large area (5 cm × 5 cm) SiPM matrix. The net photoelectron yield obtained with a preliminary configuration is approximately 4.5 photoelectrons/keV after crosstalk correction, which is rather promising in light of several planned developments. The signal-to-noise ratio and the energy threshold attainable with SiPMs is expected to improve the sensitivity for dark matter searches beyond the reach of current-generation PMT-based detectors. This result is the first proof of the viability of this technology and sets a milestone toward the design of future large-scale experiments.

Methylene Blue (MB) is combined with radiopharmaceutical for intraoperative sentinel lymph node (SLN) mapping, but its role during SLN extirpation has not been investigated yet in veterinary medicine. The aim of this study was to assess whether MB increased surgical detection of SLN beyond the use of intraoperative gamma-probe (IGP) alone in clinically node-negative dogs with mast cell tumors (MCTs) following the detection of sentinel lymphocentrums (SLCs) via preoperative planar lymphoscintigraphy. Dogs enrolled underwent MCT excision and SLC exploration guided by both MB and IGP. Data recorded for each SLN were staining (blue/non-blue), radioactivity (hot/non-hot), and histopathological status (HN0-1 vs. HN2-3). A total of 103 dogs bearing 80 cutaneous, 35 subcutaneous, and 1 mucocutaneous MCTs were included; 140 SLCs were explored, for a total of 196 SLNs removed. Associating MB with IGP raised the SLNs detection rate from 90% to 95%. A total of 44% of SLNs were metastatic: 86% were blue/hot, 7% were only blue, 5% were only hot, and 2% were non-blue/non-hot. All HN3 SLNs were hot. Combining MB with IGP can increase the rate of SLN detection in dogs with MCTs; nonetheless, all lymph nodes identified during dissection should be removed, as they might be unstained but metastatic.

Sentinel lymph node (SLN) biopsy is a well-established staging tool in canine oncology. This study aims to explore the feasibility of SLN biopsy in dogs with scars from prior excised solid malignancies that were referred for further tumor staging and/or adjuvant treatment options. Mapping was either performed using radiopharmaceutical, methylene blue, and/or near-infrared fluorescent (NIRF) imaging. Thirty-three dogs with 34 scars from prior excision of the mast cell tumor (MCT) (n = 29), soft tissue sarcoma (n = 2), oral melanoma (n = 1), subungual melanoma (n = 1), and mammary adenocarcinoma (n = 1) were retrospectively enrolled. Primary treatment consisted of curative intent/wide tumor excisions in 50.0% of dogs and marginal excision in the remaining 50.0%. The median time between tumor excision and SLN biopsy was 50 days (range 17–110 days). The procedure was successful in 31/34 scars, translating to a detection rate of 91.2%. The SLN did not correspond to the regional lymph node in 19/31 scars (61.3%). SLN metastases were histologically identified in 13/31 (41.9%) dogs, all of them affected by MCT. Based on our results, SLN biopsy using lymphoscintigraphy/methylene blue and/or NIRF is feasible in dogs presenting with scars from the prior surgical excision of solid tumors, and should be suggested for accurate nodal staging.

Purpose The onset of the coronavirus disease 19 (COVID-19) pandemic in Italy induced a dramatic increase in the need for intensive care unit (ICU) beds for a large proportion of patients affected by COVID-19-related acute respiratory distress syndrome (ARDS). The aim of the present study was to describe the health-related quality of life (HRQoL) at 90 days after ICU discharge in a cohort of COVID-19 patients undergoing invasive mechanical ventilation and to compare it with an age and sex-matched sample from the general Italian and Finnish populations. Moreover, the possible associations between clinical, demographic, social factors, and HRQoL were investigated. Methods COVID-19 ARDS survivors from 16 participating ICUs were followed up until 90 days after ICU discharge and the HRQoL was evaluated with the 15D instrument. A parallel cohort of age and sex-matched Italian population from the same geographic areas was interviewed and a third group of matched Finnish population was extracted from the Finnish 2011 National Health survey. A linear regression analysis was performed to evaluate potential associations between the evaluated factors and HRQoL. Results 205 patients answered to the questionnaire. HRQoL of the COVID-19 ARDS patients was significantly lower than the matched populations in both physical and mental dimensions. Age, sex, number of comorbidities, ARDS class, duration of invasive mechanical ventilation, and occupational status were found to be significant determinants of the 90 days HRQoL. Clinical severity at ICU admission was poorly correlated to HRQoL. Conclusion COVID-19-related ARDS survivors at 90 days after ICU discharge present a significant reduction both on physical and psychological dimensions of HRQoL measured with the 15D instrument. Trial Registration: NCT04411459.