Understanding Limits of Parametrial Resection in RadicalHysterectomy: A Randomized Controlled Trial

Cervical cancer treatment has always represented a challenge for surgeons, radiotherapist, radiologist and medical oncologist..

Smoke in the Pipe Nebula: dust emission and grain growth in the starless core FeSt 1-457

J. Forbrich, et al., “Smoke in the Pipe Nebula: dust emission and grain growth in the starless core FeSt 1-457”, Astronomy & Astrophysics, Vol 580, August 2015. This version of record is available online at: https://doi.org/10.1051/0004-6361/201425375 Reproduced with Permission from Astronomy and Astrophysics, © ESO 2016.(abridged) Methods: We derive maps of submillimeter dust optical depth and effective dust temperature from Herschel data that were calibrated against Planck. After calibration, we then fit a modified blackbody to the long-wavelength Herschel data, using the Planck-derived dust opacity spectral index beta, derived on scales of 30' (or ~1 pc). We use this model to make predictions of the submillimeter flux density at 850 micron, and we compare these in turn with APEX-Laboca observations. Results: A comparison of the submillimeter dust optical depth and near-infrared extinction data reveals evidence for an increased submillimeter dust opacity at high column densities, interpreted as an indication of grain growth in the inner parts of the core. Additionally, a comparison of the Herschel dust model and the Laboca data reveals that the frequency dependence of the submillimeter opacity, described by the spectral index beta, does not change. A single beta that is only slightly different from the Planck-derived value is sufficient to describe the data, beta=1.53+/-0.07. We apply a similar analysis to Barnard 68, a core with significantly lower column densities than FeSt 1-457, and we do not find evidence for grain growth but also a single beta. Conclusions: While we find evidence for grain growth from the dust opacity in FeSt 1-457, we find no evidence for significant variations in the dust opacity spectral index beta on scales 0.02x36x30'). The correction to the Planck-derived dust beta that we find in both cases is on the order of the measurement error, not including any systematic errors, and it would thus be reasonable to directly apply the dust beta from the Planck all-sky dust model. As a corollary, reliable effective temperature maps can be derived which would be otherwise affected by beta variations.Peer reviewe

Evaluation of efficacy of ALK inhibitors according to body mass index in ALK rearranged NSCLC patients—A retrospective observational study

No evidence exists as to whether body mass index (BMI) impairs clinical outcomes from ALK inhibitors (ALKi) in patients with ALK-rearranged non-small cell lung cancer (NSCLC). Retrospective data of patients affected by metastatic ALK-rearranged NSCLC treated with ALKi were collected. We divided patients into “low- BMI” (≤25 kg/m2) and “high- BMI” (>25 kg/m2) categories and correlated them with overall survival (OS) and progression-free survival (PFS). We included 40 patients treated with ALKi. We observed a 3-year OS of 81.5% in high-BMI vs. 49.6% in low-BMI categories (p = 0.049); the 3-year first-line PFS was superior in high-BMI vs. low-BMI patients (47% vs. 19%, p = 0.019). As expected, patients treated with Alectinib had a 55.6% 3-year PFS vs. 7.1% for others treated with ALKi (p = 0.025). High-BMI was associated with a 100% 3-year PFS rate vs. 25.4% in low-BMI Alectinib patients (p = 0.03). BMI was independently correlated with first-line PFS and OS at multivariate analysis with PS (HR 0.39, CI 95% 0.16–0.96, p = 0.042; HR 0.18, CI 95% 0.05–0.61, p = 0.006). High-BMI was associated with higher efficacy in ALK-rearranged patients. These results are particularly exciting for Alectinib and could be correlated to mechanisms that should be investigated in subsequent prospective studies

Future Perspectives in the Second Line Therapeutic Setting for Non-Oncogene Addicted Non-Small-Cell Lung Cancer

Immune checkpoint inhibitors (ICIs) have revolutionized the management of non-oncogene addicted non-small-cell lung cancer (NSCLC). Blocking the anti-PD-1 axis represents the current standard of care in the first-line setting, with drugs administered either as monotherapy or in combination with chemotherapy. Despite notable successes achieved with ICIs, most of their long-term benefits are restricted to approximately 20% of patients. Consequently, the post-failure treatment landscape after failure to first-line treatment remains a complex challenge. Currently, docetaxel remains the preferred option, although its benefits remain modest as most patients do not respond or progress promptly. In recent times, novel agents and treatment combinations have emerged, offering fresh opportunities to improve patient outcomes. ICIs combined either with antiangiogenic or other novel immunotherapeutic compounds have shown promising preliminary activity. However, more mature data concerning specific combinations do not support their benefit over standard of care. In addition, antibody–drug conjugates seem to be the most promising alternative among all available compounds according to already-published phase I/II data that will be confirmed in soon-to-be-published phase III trial data. In this report, we provide a comprehensive overview of the current second-line treatment options and discuss future therapeutic perspectives

Future Perspectives in the Second Line Therapeutic Setting for Non-Oncogene Addicted Non-Small-Cell Lung Cancer

Despite the use of novel agents in the first-line therapeutic setting, such as PD- 1/PDL1 axis blockers for non-oncogene addicted non-small-cell lung cancer, most patients with advanced disease experience progression will succumb to the illness within a short period of time. Currently, the standard second-line treatment consists primarily of systemic cytotoxic therapies, which typically yield poor outcomes. Recently, several novel therapeutic strategies have emerged that may improve patient outcomes. This article reviews current state-of-the-art treatments in this scenario and highlights potential future options.Immune checkpoint inhibitors (ICIs) have revolutionized the management of non-oncogene addicted non-small-cell lung cancer (NSCLC). Blocking the anti-PD-1 axis represents the current standard of care in the first-line setting, with drugs administered either as monotherapy or in combination with chemotherapy. Despite notable successes achieved with ICIs, most of their longterm benefits are restricted to approximately 20% of patients. Consequently, the post-failure treatment landscape after failure to first-line treatment remains a complex challenge. Currently, docetaxel remains the preferred option, although its benefits remain modest as most patients do not respond or progress promptly. In recent times, novel agents and treatment combinations have emerged, offering fresh opportunities to improve patient outcomes. ICIs combined either with antiangiogenic or other novel immunotherapeutic compounds have shown promising preliminary activity. However, more mature data concerning specific combinations do not support their benefit over standard of care. In addition, antibody–drug conjugates seem to be the most promising alternative among all available compounds according to already-published phase I/II data that will be confirmed in soon-to-bepublished phase III trial data. In this report, we provide a comprehensive overview of the current second-line treatment options and discuss future therapeutic perspectives.Depto. de MedicinaFac. de MedicinaTRUEpubDescuento UC

Circulating CD137+T cells as an immune biomarker for response to anti-PD1 immunotherapy in NSCLC patients

Anti-PD1 treatment, administered alone (PDL1>50%) or in combination with chemotherapy (PDL1<50%), is the standard of care in the first-line setting in non-oncogenic addicted Non-Small Cell Lung Cancer (NSCLC). Despite the success of these treatments, only 20-30% of these patients fully respond to these therapies, highlighting the need to identify novel biomarkers to optimize treatment strategies. CD137+ T cells are identified as activated and tumor-specific T cells. In several solid tumors, their levels correlate with responses to anti-PD1 therapy. In this study, we evaluate the levels of CD137+ T cells in NSCLC patients as biomarker of response to immunotherapy. PBMCs derived from 82 NSCLC patients undergoing both first- (from 2020-today) and second-line (from 2016 to 2019) anti-PD1 treatment were analyzed at baseline by cytofluorimetry for the expression of CD3, CD4, CD8, CD137, and PD1 molecules. These parameters were correlated with clinical outcomes. Results show that in all patients, the levels of circulating CD137+T cells are significantly higher in responder patients (Rs) than in non-responders (NRs) (p=0.02), and that these high levels were ascribed to both CD8 (p=0.02) and CD4 (p=0.03) T cell populations. Moreover, patients with a percentage of CD3+CD137+>1.26% had prolonged OS (p=0.007) and PFS (p=0.002). Rs also showed high levels of CD137+PD1+T cells compared with NR (p=0.002) ascribed to both CD8 and CD4 T cells (p=0.02 and p=0.03, respectively). Patients undergoing first- and second-line treatment were further analyzed and compared. The group of patients receiving first-line therapy had higher levels of CD137+ (p=0.005) and CD137+PD1+ (p<0.001) T cells compared with the other group, suggesting that naïve patients had a more activated immune system. Our results indicate that levels of circulating CD137+ T cells could predict the response to anti-PD1 therapy in NSCLC patients and could be used as biomarker for the success of anticancer treatmen

Impact of Hysterotomy Closure Technique on Subsequent Cesarean Scar Defects Formation: A Systematic Review

The uterine caesarean scar defect, also known as uterine niche or isthmocele, is an irregularity in the anterior uterine wall at the site of a previous cesarean section scar. It is associated with obstetrical complications such as caesarean scar, ectopic pregnancy, uterine rupture, and the placenta accreta spectrum. Women with cesarean scar defects are frequently asymptomatic but may also experience abnormal vaginal bleeding, chronic pelvic pain, and infertility. This systematic review aims to determine the best hysterotomy closure technique to prevent subsequent development of uterine scar defects. An electronic search in Medline, Embase, Cochrane Database of Systematic Reviews, ClinicalTrials.gov was performed from January 2001 until December 2020 for studies evaluating hysterotomy closure techniques. Our systematic search strategy identified 1,781 titles. Six studies fulfilled inclusion criteria and were included in the final analysis. The results supported the superiority of the double-layer closure over the single-layer closure. Hysterotomy closure with continuous running sutures in two layers represents a suitable option to prevent cesarean scar defect formation. Particularly, the first layer should include the decidua and the second layer should overlap the first

MITO: A 2.6-m mm/sub-mm ground based telescope

MITO is a multi-purpose experiment mainly finalized for sub/mm cosmological observations. Here we describe essentially the SZ-meter version specifically dedicated to photometric measurements of the Sunyaev-Zel'dovich effect towards near and large clusters. The instrumentation consists of a 2.6 meter in diameter ground-based flux collector located at the top of the Testa Grigia mountain (3480 m a.s.l. AO - Italy). A single-pixel photometer (17 arcmin FWHM) operating at 150, 209, 270 and 335 GHz cools down four bolometric detectors to 290 mK for 4 nights continuously by a double stage He-3-He-4 fridge. An electromechanical system allows for a field of view sky modulation with several profiles and high duty cycle limiting the microphonic noise on the detectors. Atmospheric fluctuations are thus reduced by means of triple-beam subreflector spatial modulation and synchronous demodulation

Advanced non-small-cell lung cancer: how to manage EGFR and HER2 exon 20 insertion mutation-positive disease

EGFR exon 20 insertion mutations (Ex20ins) and HER2 mutations characterize an oncogene-addicted subtype of non-small-cell lung cancer (NSCLC) typically associated with a never or light smoking history, female sex, and adenocarcinoma histology. Nevertheless, Ex20ins-mutant and HER2-mutant advanced NSCLCs are still difficult to treat for various reasons. First, there is a need for sophisticated diagnostic tools (e.g. next-generation sequencing) that could allow the identification of these relatively rare molecular drivers. Second, highly active targeted drugs that might support a significant change in patients' prognosis when used as first-line therapy are required. In fact, although a few targeted drugs have so far demonstrated antitumour activity for these patients, mainly selective human epidermal receptor-tyrosine kinase inhibitors such as poziotinib and mobocertinib (for both molecular alterations), monoclonal antibodies such as amivantamab (for Ex20ins), and antibody-drug conjugates such as trastuzumab deruxtecan (for HER2 mutants), they are mostly confined for clinical use in pretreated patients. Finally, Ex20ins-targeted or HER2-targeted drugs might be difficult to access in different countries or regions worldwide. In the present review, we provide a concise but comprehensive summary of the challenges that lie ahead as we move towards personalized treatment of Ex20ins-mutant and HER2-mutant advanced NSCLC, also suggesting a treatment algorithm that could be followed for patients with these genetic aberrations