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We retrospectively analyzed real-world data from the ARON-1 project for patients with papillary renal cell carcinoma who received first-line immune-based combinations or tyrosine kinase inhibitors. Immune-based combinations were associated with better 1-yr and 2-yr overall survival rates, better median progression-free survival, and a better objective response rate. Immune-based combinations are the preferable option for first-line treatment in this setting.

The realization of efficient optical devices depends on the ability to harness strong nonlinearities, which are challenging to achieve with standard photonic systems. Exciton–polaritons formed in hybrid organic–inorganic perovskites offer a promising alternative, exhibiting strong interactions at room temperature (RT). Despite recent demonstrations showcasing a robust nonlinear response, further progress is hindered by an incomplete understanding of the microscopic mechanisms governing polariton interactions in perovskite-based strongly coupled systems. Here, we investigate the nonlinear properties of quasi-2D dodecylammonium lead iodide perovskite (n3-C12) crystals embedded in a planar microcavity. Polarization-resolved pump–probe measurements reveal the contribution of indirect exchange interactions assisted by dark states formation. Additionally, we identify a strong dependence of the unique spin-dependent interaction of polaritons on sample detuning. The results are pivotal for the advancement of polaritonics, and the tunability of the robust spin-dependent anisotropic interaction in n3-C12 perovskites makes this material a powerful choice for the realization of polaritonic circuits.

ABSTRACTIntroductionThe therapeutic scenario of metastatic hormone-sensitive prostate cancer (mHSPC) has dramatically changed in recent years, with the approval of new-generation Androgen Receptor Signaling Inhibitors (ARSIs), in combination with the androgen deprivation therapy (ADT), which was the previous standard of care. Despite showing a similar clinical efficacy, ARSIs, all of which are administered orally, are different in terms of pharmacokinetic and drug-drug interactions (DDIs).Areas coveredThis review covers the main pharmacokinetic characteristics of ARSIs that have been approved for the first-line therapy of mHSPC patients, underlying the differences among these molecules and focusing on the known or possible interactions with other drugs. Full-text articles and abstracts were searched in PubMed.Expert opinionSince prostate cancer occurs mainly in older age, comorbidities and the consequent polypharmacy increase the DDI risk in mHSPC patients who are candidates for ARSI. Waiting for new therapeutic options, in the absence of direct comparisons, pharmacokinetic knowledge is essential to guide clinicians in prescribing ARSI in this setting.

The GOG240 trial established bevacizumab with chemotherapy as standard first-line therapy for metastatic or recurrent cervical cancer. In the BEATcc trial (ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030), we aimed to evaluate the addition of an immune checkpoint inhibitor to this standard backbone.

Background: Currently, several therapies are available for metastatic castration-resistant prostate cancer (mCRPC) but no specific clinical factors to personalize treatment. We first sought the prognostic value of duration on androgen-deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC) in patients receiving androgen-receptor-signaling inhibitors (ARSI) for mCRPC. Methods: A multicenter cohort of mCRPC patients who started ARSI between July 2011 and October 2021 was identified. Based on their initial disease burden and duration on ADT for HSPC, primary progressive (PP) men were classified into four groups: low/intermediate-risk localized disease (LOC) and high-risk localized/locally advanced disease (LAD) and short-term (ST) < 24 vs. long-term (LT) ADT ≥ 24 months, whereas de novo (DN) mHSPC were subdivided into short-time vs. long-time to CRPC. Results: We included 919 mCRPC patients with a median age of 77 years [interquartile range (IQR) = 71–82)]. Median ADT duration in HSPC was 24 months (IQR = 14–40). Median follow-up was 91 months (IQR = 62–138), median OS and PFS from ARSI start were 20 (IQR 10–32) and 10 months (IQR = 5–19), respectively. In PP developing metastatic disease (n= 655, 71.3%), LOC and LAD with ST ADT had a greater than almost double-risk of death compared to LT ADT (LOC/ST: hazard ratio [HR] = 2.01; 95% CI 1.54–2.64; LAD/ST: HR = 1.73; 95% CI 1.34–2.24; p< 0.001). In the multivariate analysis including age, prognostic cohort, Gleason, ECOG, radical radiotherapy and prostatectomy, groups with ST ADT were associated with worse OS compared to LT ADT (LOC/ST: HR = 1.84; 95% CI 1.38–2.45; p< 0.001; LAD/ST: HR = 1.59; 95% CI 1.21–2.10; p< 0.001), along with ECOG > 2 (HR = 1.55; 95% CI 1.06–2.26; p= 0.03). There were also similar results of PFS. Moreover, long-time to CRPC in patients with history of DN mHSPC (n= 264, 28.7%) resulted in a better OS/PFS (HR = 0.76, 95% CI 0.56–1.02, p= 0.064 and HR = 0.74, 95% CI 0.55–0.99, p= 0.042, respectively). Conclusions: Our study showed that duration on ADT for mHSPC was significantly associated with survival in mCRPC undergoing ARSI. These findings suggest a possible connection between initial management of prostate tumour and a better prognostication in mCRPC. Prospective trials are warranted.

Aim: This study aimed to assess the potential role of physical activity (PA) in reducing the risk of developing inflammatory bowel diseases (IBDs) and in their management. Subject and methods: A systematic review of literature was conducted up to October 2023 using the PubMed, Scopus, Web of Science and Cochrane Library databases. Observational studies, semi-experimental and experimental studies reporting PA effects were considered eligible. Data on disease status and PA characteristics, main outcomes and possible confounders were collected in a database. The Newcastle–Ottawa Quality Assessment Scale was used to assess risk of bias. Results: Of the 29 articles included, six investigated PA and risk of IBDs and four of them showed an inverse relationship. Among the others, seven reported positive effects of PA on IBD symptoms, while all showed improvements in comorbidities, complications and quality of life. Conclusion: PA seems to be effective in preventing or treating IBDs and their complications. Owing to the low quality of the majority of the studies and their heterogeneity, further research is needed to better understand which type and level of PA may be useful in the prevention and treatment of these diseases.

Topological bound states in the continuum are confined wave-mechanical objects that offer advantageous ways to enhance light–matter interactions in compact photonic devices. In particular, their large quality factor in the strong-coupling regime has recently enabled the demonstration of Bose–Einstein condensation of bound-state-in-the-continuum polaritons. Here we show that polariton condensation into a negative-mass bound state in the continuum exhibits interaction-induced state confinement, opening opportunities for optically reprogrammable molecular arrays of quantum fluids of light. We exploit this optical-trapping mechanism to demonstrate that such artificial molecular complexes show hybridization into macroscopic modes with unusual topological charge multiplicity. Additionally, we demonstrate the scalability of our technique by constructing extended mono- and diatomic chains of bound-state-in-the-continuum polariton fluids that display non-Hermitian band formation and the opening of a minigap. Our findings offer insights into large-scale, reprogrammable, driven, dissipative many-body systems in the strong-coupling regime.

Preclinical evidence has suggested an interplay between the androgen receptor, which largely drives the growth of prostate cancer cells, and poly(ADP-ribose) polymerase. This association provides a rationale for their co-inhibition for the treatment of metastatic castration-resistant prostate cancer (mCRPC), an area of unmet medical need. The phase 3 TALAPRO-2 study investigated combining the poly(ADP-ribose) polymerase inhibitor talazoparib with enzalutamide versus enzalutamide alone as first-line treatment of mCRPC. Patients were prospectively assessed for tumor alterations in DNA damage response genes involved in homologous recombination repair (HRR). Two cohorts were enrolled sequentially: an all-comers cohort that was enrolled first (cohort 1; N= 805 (169 were HRR-deficient)), followed by an HRR-deficient-only cohort (cohort 2; N= 230). We present results from the alpha-controlled primary analysis for the combined HRR-deficient population (N= 399). Patients were randomized in a 1:1 ratio to talazoparib or placebo, plus enzalutamide. The primary endpoint, radiographic progression-free survival, was met (median not reached at the time of the analysis for the talazoparib group versus 13.8 months for the placebo group; hazard ratio, 0.45; 95% confidence interval, 0.33 to 0.61; P< 0.0001). Data for overall survival, a key secondary endpoint, are immature but favor talazoparib (hazard ratio, 0.69; 95% confidence interval, 0.46 to 1.03; P= 0.07). Common adverse events in the talazoparib group were anemia, fatigue and neutropenia. Combining talazoparib with enzalutamide significantly improved radiographic progression-free survival in patients with mCRPC harboring HRR gene alterations, supporting talazoparib plus enzalutamide as a potential first-line treatment for these patients. ClinicalTrials.gov Identifier: NCT03395197.

Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immuno-oncology agents (IO+IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as first-line therapy for metastatic renal cell carcinoma (mRCC).

Introduction: Low molecular weight heparin (LMWH) has been the backbone of the treatment of cancer associated thrombosis (CAT). Direct-acting oral anticoagulants (DOACs) have shown efficacy and safety not inferior to LMWH and guidelines included DOACs as an option for CAT treatment. Nevertheless, DOACs are still poorly prescribed in patients with cancer. The aim of this survey was to better understand prescription patterns of anticoagulants, in particular of DOACs, especially in gynecological cancers (GCs).Methods: Our survey was made up of 21 questions, the last four questions addressed to medical doctors (MDs) involved in GCs. An invitation to complete the survey was sent by e-mail to 691 MITO (Multicentre Italian Trials in Ovarian cancer and gynaecologic malignancies) and 2093 AIOM (Associazione Italiana di Oncologia Medica) members.Results: Overall, 113 MDs completed the questionnaire, 69 involved in GCs. Most respondents (46, 41%) were aged 30-40 years old, worked in public hospitals (59, 52.2%), were medical oncologists (86, 76.1%). LMWH was the preferred choice for the treatment of CAT (104, 92%). However, 89 respondents (78.8%) prescribed or asked to prescribe a DOAC for CAT. The major concern about DOACs was the difficulty in verifying the therapeutic effect and the absence of antidotes in case of bleeding (37.9%). In patients with GCs, DOACs were used with niraparib, olaparib, rucaparib and immune checkpoint inhibitors (ICIs) in less than 10 patients by 23%, 20%, 9% and 10.2% of respondents, respectively.Conclusion: The responders are aware of the Direct-acting oral anticoagulants option and would like to use them

Despite the age of the Restoration, through a toxic Romanticism, was at the origin of nationalistic, irrational and warlike currents, sometimes with possible racist developments in several areas of Europe, in Italy, during the same Restoration, there was on the contrary an initial emergence, within Catholic culture, of spiritual and ethical-political visions centered on peace. In this essay, reflecting on several works of Rosmini, the great Italian philosopher and classical liberal priest, and on his great friend, the writer and Catholic liberal Alessandra Manzoni, we see the birth and development of this original vision of European peace, founded on education, religion and love. [ABSTRACT FROM AUTHOR]

In this work, the authors aim at developing a reliable and fast methodology to evaluate the wear evolution in tire starting from a complete optical 3D scanning. Starting from a data cloud, a semi-automatic methodology was implemented in MATLAB to extract mean tread radial profiles in correspondence of the desired angular position of the tire. These profiles could be numerically evaluated to establish the presence of irregular wear and the characteristic parameter of the groove depth. The reliability and the robustness of this methodology was firstly tested by applying it to several synthetic case studies modeled in CATIA V5®, where ovalization and presence of defects were also simulated. The groove depth was determined with an error lower than 1% for the ideal model, while the introduction of ovalization and defects leaded to an error of 2.6% in the worst condition. In a second time, the methodology has been successfully applied to experimental measurements carried out in two different wear life of the tire, allowing the tracking of the wear phenomena through the evaluation of the progressive lowering of tread radial profiles.

Co-inhibition of poly(ADP-ribose) polymerase (PARP) and androgen receptor activity might result in antitumour efficacy irrespective of alterations in DNA damage repair genes involved in homologous recombination repair (HRR). We aimed to compare the efficacy and safety of talazoparib (a PARP inhibitor) plus enzalutamide (an androgen receptor blocker) versus enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC).

Background: First-line therapies based on immune-checkpoint inhibitors (ICIs) significantly improved survival of metastatic renal cell carcinoma (mRCC) patients. Cabozantinib was shown to target kinases involved in immune-escape and to prolong survival in patients pre-treated with tyrosine-kinase-inhibitors (TKIs). The impact of ICIs combinations in first line on subsequent therapies is still unclear.Methods: This is an open label, multicenter, single arm, phase II study designed to assess activity, safety and efficacy of cabozantinib in mRCC patients progressed after an adjuvant or first line anti-Programmed Death (PD)-1/PD-Ligand (PD-L) 1-based therapy. Primary endpoint was progression free survival (PFS), secondary endpoints were overall survival (OS), objective response rate (ORR) and safety.Results: 31 patients were included in the analysis. After a median (m) follow-up of 11.9 months, mPFS was 8.3 months (90%CI 3.9-17.4) and mOS was 13.8 months (95%CI 7.7-29.0). ORR was 37.9% with an additional 13 patients achieving disease stability. Grade 3-4 adverse events occurred in 47% of patients, including more frequently creatine phosphokinase (CPK) serum level elevation, neutropenia, hyponatremia, diarrhea, hand-food syndrome, oral mucositis and hypertension.Conclusions: The BREAKPOINT trial met its primary endpoint showing that cabozantinib as second line therapy after ICIs was active in mRCC. Safety profile was manageable.Trial registration number: NCT03463681 - A Study of CaBozantinib in Patients With Advanced or Unresectable Renal cEll cArcinoma (BREAKPOINT) - https://clinicaltrials.gov/ct2/show/NCT03463681

The results of the geophysical surveys carried out in the city of Ugento, specifically in the St. Antonio area and into the Medieval Castle, are presented in this paper. The aim of this study is to integrate the results of Ground-Penetrating Radar and Electrical Resistivity Tomography surveys in order to support archaeological investigations aimed at the elaboration of a detailed archaeological map of the Messapian, Roman and Medieval settlement. Indeed, the obtained data were jointly analysed with archaeological data already known and were georeferenced on the general plans of the site in order to obtain an overall view of the anomalies detected by geophysical instrumentation and related to buried ancient structures. In particular, the geophysical surveys carried out in the St. Antonio area made it possible to reconstruct a stretch of the Messapian city walls and nearby necropolis, while the investigations inside the Castle allowed for the acquisition of very interesting data about previous phases dated to the Middle Ages (and maybe also the Messapian or Roman ages) and about the geo-morphological characteristics of the site.

A concomitant drug-based score was developed by our group and externally validated for prognostic and predictive purposes in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). The model considers the use of three classes of drugs within a month before initiating ICI, assigning score 1 for each between proton pump inhibitor and antibiotic administration until a month before immunotherapy initiation and score 2 in case of corticosteroid intake. In the present analysis, the drug score was validated in a prospective population of 305 patients with metastatic renal cell carcinoma treated with ipilimumab plus nivolumab in the first-line setting. The value of the model in predicting overall survival and progression-free survival was statistically significant and clinically meaningful, with an overall survival rate at 12 months of 73% vs. 44% (P<0.0001), and median progression-free survival of 11.6 (95% CI: 9.1–14.1) months versus 4.8 (95% CI: 2.7–7.0) months (P=0.002), respectively, for patients belonging to the favorable group (score 0–1) versus the unfavorable (score 2–4). Further development will be represented by the gut microbiome analysis according to the drug-based model classification and to the outcome of patients to ICI therapy to demonstrate the link between drug exposure and immune sensitivity.

Tyrosine kinase inhibitors (TKIs) are the backbone of the systemic treatment for patients with metastatic renal cell carcinoma (mRCC). TKIs such as pazopanib and cabozantinib can interact with other drugs concomitantly administered, particularly with proton-pump inhibitors (PPIs), possibly impacting the effectiveness of the anticancer treatment and patients outcome. Few data are available about this interaction. We conducted a multicenter retrospective observational data collection of patients with mRCC treated with pazopanib or cabozantinib between January 2012 and December 2020 in nine Italian centers. Univariate and multivariate analyses were performed. The aim was to describe the impact of baseline concomitant PPIs on the outcome of patients to pazopanib and cabozantinib in terms of response, progression-free survival (PFS) and overall survival (OS), toxicity, and treatment compliance. The use of PPI in our study population (301 patients) significantly influenced the effectiveness of TKIs with worse PFS (16.3 vs. 9.9 months; P< 0.001) and OS (30.6 vs. 18.4 months; P= 0.013) in patients taking PPI at TKI initiation. This detrimental effect was maintained both in the pazopanib and cabozantinib groups. The use of PPI influenced the toxicity and TKI treatment compliance with a reduction of dose or schedule modifications, and treatment interruptions in the population taking PPIs. Our study demonstrates that the use of PPIs can significantly influence the outcome and compliance of patients with mRCC to TKI treatment, suggesting the importance of a more careful selection of patients who need a gastroprotective therapy, avoiding indiscriminate use of PPIs.

Exciton–polaritons derived from the strong light–matter interaction of an optical bound state in the continuum with an excitonic resonance can inherit an ultralong radiative lifetime and significant nonlinearities, but their realization in two-dimensional semiconductors remains challenging at room temperature. Here we show strong light–matter interaction enhancement and large exciton–polariton nonlinearities at room temperature by coupling monolayer tungsten disulfide excitons to a topologically protected bound state in the continuum moulded by a one-dimensional photonic crystal, and optimizing for the electric-field strength at the monolayer position through Bloch surface wave confinement. By a structured optimization approach, the coupling with the active material is maximized here in a fully open architecture, allowing to achieve a 100 meV photonic bandgap with the bound state in the continuum in a local energy minimum and a Rabi splitting of 70 meV, which results in very high cooperativity. Our architecture paves the way to a class of polariton devices based on topologically protected and highly interacting bound states in the continuum.

Immune checkpoint inhibitor (ICI)-based combinations have become the first-line standard of care in metastatic renal cell carcinoma (mRCC), but their activity on the primary tumor is still one of the most debated issues.

The results of the geophysical surveys carried out in 2019 in the Abbey of Santa Maria di Cerrate (Lecce) are presented in this paper. The objective of this study was to achieve a better knowledge of the site, since it was only partially investigated by small archaeological excavation samples. The geophysical measurements were conducted inside and outside the church in order to identify buried ancient structures, using both the georadar and geoelectrical survey methodologies. The results of GPR (ground-penetrating radar), ERT (electrical resistivity tomography) and IP (induced polarisation) were jointly analysed with archaeological data already known and were georeferenced on the general plans of the site in order to obtain an overall view of the anomalies detected by geophysical instrumentation and probably linked to buried ancient structures.

Numerical simulations of steady and unsteady viscous flows are presented by adopting two different numerical methodologies: the Smoothed Particle Hydrodynamics formulation implemented in the open-source code DualSPHysics and an in-house lattice Boltzmann code based on a concise central-moments scheme. Both methods employ a weakly compressible assumption to simulate incompressible flow, which means the fluid is assumed barotropic and the density and pressure are related through an equation of state. The accuracy of the two approaches is evaluated against well-defined and consolidated benchmark tests. Advantages and disadvantages of the two methodologies are discussed and substantiated by quantitative comparisons that focus on accuracy and efficacy of the two methodologies against other well-established computational methods. Overall, both formulations proposed herein are able to capture the relevant flow physics with a good level of accuracy when compared to other more affirmed techniques. Remarkably, this is observed in spite of the proposed two methods lacking key strategies commonly used in grid-based methods, such as adaptive mesh refinement.

Fecal microbiota transplantation (FMT) is highly effective against recurrent Clostridioides difficileinfection and is considered a promising treatment for other microbiome-related disorders, but a comprehensive understanding of microbial engraftment dynamics is lacking, which prevents informed applications of this therapeutic approach. Here, we performed an integrated shotgun metagenomic systematic meta-analysis of new and publicly available stool microbiomes collected from 226 triads of donors, pre-FMT recipients and post-FMT recipients across eight different disease types. By leveraging improved metagenomic strain-profiling to infer strain sharing, we found that recipients with higher donor strain engraftment were more likely to experience clinical success after FMT (P= 0.017) when evaluated across studies. Considering all cohorts, increased engraftment was noted in individuals receiving FMT from multiple routes (for example, both via capsules and colonoscopy during the same treatment) as well as in antibiotic-treated recipients with infectious diseases compared with antibiotic-naïve patients with noncommunicable diseases. Bacteroidetes and Actinobacteria species (including Bifidobacteria) displayed higher engraftment than Firmicutes except for six under-characterized Firmicutes species. Cross-dataset machine learning predicted the presence or absence of species in the post-FMT recipient at 0.77 average AUROC in leave-one-dataset-out evaluation, and highlighted the relevance of microbial abundance, prevalence and taxonomy to infer post-FMT species presence. By exploring the dynamics of microbiome engraftment after FMT and their association with clinical variables, our study uncovered species-specific engraftment patterns and presented machine learning models able to predict donors that might optimize post-FMT specific microbiome characteristics for disease-targeted FMT protocols.

This paper reports the results of the integrated geophysical surveys performed inside the Monastery of St Chiara in Nardó in southern Italy. Ground-penetrating radar (GPR) and electrical resistivity tomography (ERT) investigations were carried out to find the tomb of Sister Chiara D’Amato, whose location has been lost over the centuries. Sister Chiara Isabella D'Amato was a charismatic and holy figure. She died in 1693. She was buried inside the monastery but her body has never been found. The data acquisition was performed along with a series of closely spaced lines for GPR and using a non-standard array for ERT. Data were processed and visualised as two-dimensional vertical sections and depth slices or three-dimensional volumes (GPR and ERT) to allow an integrated interpretation of the geophysical results. The analysis of the geophysical data sets revealed a series of anomalies that could be ascribed possible archaeological structures, probably related to the earliest ages of the sacred building as well as other anomalies (bedrock, fractures) of presumable natural origin. In particular, one geophysical anomaly was suspected of being connected to burial and consequently further investigated with the use of a video endoscope. The results reveal the presence of a void but it has not yet been clarified whether it is the burial of Sister Chiara or not as it is awaiting the excavation.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2006.03.068 Byline: Paolo Vercellini, Giuliana Pietropaolo, Olga De Giorgi, Raffaella Daguati, Roberta Pasin, Pier Giorgio Crosignani Abstract: This study was undertaken to ascertain whether the incidence of pregnancy is increased and time-to-conception is reduced in infertile women with rectovaginal endometriosis undergoing conservative surgery compared with those on expectant management. Author Affiliation: Benign Gynecologic Surgery Unit, Clinica Ostetrica e Ginecologica II, University of Milan, Istituto 'Luigi Mangiagalli,' Milan, Italy Article History: Received 28 July 2005; Revised 23 January 2006; Accepted 19 March 2006 Article Note: (footnote) Reprints not available from the authors.

Controversial data are available on the association between the retrovirus-like long-terminal repeat (LTR) DQ-LTR13 and genetic susceptibility to type 1 diabetes and other autoimmune diseases. We analyzed DNA samples from 315 type 1 diabetic patients, 166 autoimmune Addison's disease (AAD) patients, 1,054 healthy subjects, and 144 families of type 1 diabetic offspring. DQ-LTR13 was more frequent among patients than healthy subjects ([P.sub.c] < 0.0006), and a preferential transmission of DQB1*0302-[LTR13.sup.+] from parents to type 1 diabetic offspring was observed. DQ-LTR13 was in linkage disequilibrium (LD) with DQB1*0302 but not DQB1*0201. The presence of DQ-LTR13 increased the odds ratio of DQB1*0302 2.9- to 3.2-fold for type 1 diabetes and AAD. DRB1*0403 was absent in all of the 169 DRB1*04-positive patients but present in 27% (34 of 127) DRB1*04-positive healthy subjects ([P.sub.c] < 0.001). DQ-LTR13 was detected in 1 of 34 (3%) DRB1*0403-positive healthy subjects and 36 of 93 (39%) individuals carrying another DRB1*04 allele ([P.sub.c] = 0.002). Multivariate logistic regression analysis revealed that DQ-LTR13 is not independently associated with type 1 diabetes and AAD after correction for DQB1*0302 and DRB1*0403. Conversely, DQBI*0201, DQB1*0302, DRB1*0401, and DRB1*0403 were all significantly associated with disease risk also after correction for DQ-LTR13. We provide conclusive evidence that the genetic association of DQ-LTR13 with type 1 diabetes and AAD is primarily due to a LD with DQB1*0302 and DRB1*0403., Human endocrine autoimmune diseases, which include type 1 diabetes, autoimmune Addison's disease (AAD), thyroid diseases, autoimmune hypophysitis, hypoparathyroidism, and premature ovarian failure, are complex genetic traits with major contribution of [...]

The authors have investigated the hypothesis that coagulation or laser vaporization of endometriomas can increase ovarian cyst recurrence risk. Results have demonstrated that without excision coagulation or laser vaporization seem to increase cyst recurrence risk.

Bound states in the continuum (BICs)1–3are peculiar topological states that, when realized in a planar photonic crystal lattice, are symmetry-protected from radiating in the far field despite lying within the light cone4. These BICs possess an invariant topological charge given by the winding number of the polarization vectors5, similar to vortices in quantum fluids such as superfluid helium and atomic Bose–Einstein condensates. In spite of several reports of optical BICs in patterned dielectric slabs with evidence of lasing, their potential as topologically protected states with theoretically infinite lifetime has not yet been fully exploited. Here we show non-equilibrium Bose–Einstein condensation of polaritons—hybrid light–matter excitations—occurring in a BIC thanks to its peculiar non-radiative nature, which favours polariton accumulation. The combination of the ultralong BIC lifetime and the tight confinement of the waveguide geometry enables the achievement of an extremely low threshold density for condensation, which is reached not in the dispersion minimum but at a saddle point in reciprocal space. By bridging bosonic condensation and symmetry-protected radiation eigenmodes, we reveal ways of imparting topological properties onto macroscopic quantum states with unexplored dispersion features. Such an observation may open a route towards energy-efficient polariton condensation in cost-effective integrated devices, ultimately suited for the development of hybrid light–matter optical circuits.

Bladder detrusor endometriosis appears to occur when endometrial cells from inside the uterus flow out of the Fallopian tubes and land on the bladder. This was the conclusion of a study of 40 women. There was no association between bladder detrusor endometriosis and uterine adenomyosis.

IMPORTANCE: Interim analyses of the IMmotion151 trial (A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma) reported improved progression-free survival (PFS) for patients with programmed death ligand 1–positive (PD-L1+) metastatic renal cell carcinoma (mRCC) receiving the PD-L1 inhibitor atezolizumab plus the vascular endothelial growth factor (VEGF) inhibitor bevacizumab vs the receptor tyrosine kinase inhibitor sunitinib. Overall survival (OS) results were immature at interim analyses. OBJECTIVE: To report the final OS results, safety, and exploratory biomarker analyses of the association of transcriptomic subgroups with OS in the IMmotion151 trial. DESIGN, SETTING, AND PARTICIPANTS: IMmotion151 was a multicenter, open-label, phase 3 randomized clinical trial that compared the efficacy and safety of atezolizumab plus bevacizumab vs sunitinib in patients with untreated mRCC. IMmotion151 included patients from 152 academic medical centers and community oncology practices in 21 countries. Adult patients with mRCC with components of clear cell or sarcomatoid histologic features, measurable disease (according to Response Evaluation Criteria in Solid Tumors, version 1.1), adequate performance status, hematologic and end organ function, and tumor tissue available for PD-L1 testing were included. IMmotion151 was initiated on May 20, 2015, and the study is ongoing. This final analysis was performed from May 20, 2015, to February 14, 2020. INTERVENTIONS: Receipt of 1200 mg of intravenous (IV) atezolizumab every 3 weeks and 15 mg/kg of IV bevacizumab every 3 weeks or 50 mg orally once daily of sunitinib (4 weeks on and 2 weeks off). MAIN OUTCOMES AND MEASURES: The coprimary end points were PFS (previously reported) in patients with PD-L1+ disease and OS in the intention-to-treat population. Additional exploratory outcomes included OS in the PD-L1+ population, association with transcriptomic subgroups, and safety. RESULTS: The IMmotion151 trial assessed 915 patients with metastatic renal cell carcinoma. Mean (IQR) age was 62 (56-69) years for patients receiving atezolizumab plus bevacizumab and 60 (54-66) years for patients receiving sunitinib; 669 (73.1%) were male and 246 (26.9%) were female. The final analysis showed similar median OS in patients receiving atezolizumab plus bevacizumab vs sunitinib in the intention-to-treat (36.1 vs 35.3 months) and PD-L1+ (38.7 vs 31.6 months) populations. No new safety signals were reported. The additional exploratory outcome of atezolizumab plus bevacizumab vs sunitinib showed improved median OS trends in patients whose tumors were characterized by T-effector/proliferative, proliferative, or small nucleolar RNA transcriptomic profiles (35.4 vs 21.2 months; hazard ratio, 0.70; 95% CI, 0.50-0.98). CONCLUSIONS AND RELEVANCE: The primary end point of PFS was met at interim analyses, although no improvement in OS was observed with atezolizumab plus bevacizumab at the final analysis. Biomarker analyses provided insight into which patients with mRCC may benefit from combined anti−PD-L1 and anti-VEGF therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02420821

Eruptive melanocytic nevi (EMN) describes the sudden onset of cutaneous nevi over weeks or months. Such a clinical event is generally seen in young adult patients and may be related to several possible causes. We report here a case of EMN in an old male patient followed up for a thick amelanotic cutaneous melanoma. A few months after the eruption, multiple hepatic masses, diagnosed as melanoma metastasis, were detected. The presented case may suggest that EMN may be a paraneoplastic phenomenon of alert in patients being followed for melanoma or other malignancies.

Women with excess menstrual bleeding appear to find surgically removing the uterus through the vagina slightly more preferable in the long-term than surgically removing uterine lining sections. Questionnaires addressing surgery satisfaction, quality of life, and sexual functioning were completed by 77 women two years after having one of these two surgeries. Overall, 94.8% of the women with vaginal hysterectomies and 86.8% of the women with lining removal were satisfied or very satisfied with their surgery. More women with vaginal hysterectomies reported high quality of life scores. Sexual function was similar in the two groups.

Byline: Paolo Vercellini, Olga De Giorgi, Sabina Oldani, Ilenia Cortesi, Stefania Panazza, Pier Giorgio Crosignani Keywords: Endometriosis; pelvic pain; depot medroxyprogesterone acetate; oral contraceptives; danazol Abstract: OBJECTIVE: Our purpose was to evaluate the efficacy and safety of depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol in the long-term treatment of pelvic pain in women with endometriosis. STUDY DESIGN: Eighty patients with endometriosis and moderate or severe pelvic pain were randomized to treatment for 1 year with intramuscular depot medroxyprogesterone acetate 150 mg every 3 months or a cyclic monophasic oral contraceptive (ethinyl estradiol 0.02 mg, desogestrel 0.15 mg) combined with oral danazol 50 mg a day for 21 days of each 28-day cycle. The women were asked to grade the degree of their satisfaction at the end of therapy. Variations in severity of symptoms during treatment were determined by a 10 cm visual analog and a 0- to 3-point verbal rating scale. RESULTS: Twenty nine of 40 subjects (72.5%) in the depot medroxyprogesterone acetate group were satisfied after 1 year of therapy compared with 23 of 40 (57.5%) in the oral contraceptive plus danazol group (I.sup.2.sub.1 = 1.37, p = 0.24, odds ratio 1.95, 95% confidence interval 0.76 to 4.97). A significant decrease was observed in all symptom scores in both study groups. At 1-year assessment dysmenorrhea was significantly greater in women allocated to oral contraceptive plus danazol. CONCLUSION: Depot medroxyprogesterone acetate seems to be an effective, safe, and convenient low-cost treatment for pelvic pain associated with endometriosis. However, women should be carefully counseled regarding menstrual changes and the potential prolonged delay in the return of ovulation. (Am J Obstet Gynecol 1996;175:396-401.) Author Affiliation: Milan, Italy Article History: Received 18 October 1995; Revised 1 December 1995; Accepted 29 January 1996 Article Note: (footnote) [star] From Clinica Ostetrica e Ginecologica ''Luigi Mangiagalli,'' University of Milano., [star][star] Reprint requests: Paolo Vercellini, MD, Clinica Ostetrica e Ginecologica 'Luigi Mangiagalli' dell' Universita di Milano, Via Commenda 12, 20122 Milano, Italy., a 0002-9378/96 $5.00 + 0 6/1/72362

Rates of Hepatitis C virus (HCV) testing and diagnosis are variable among people who use drugs (PWUD). In Puglia in 2018, of 871 subjects screened, 38% had HCV antibodies (HCVAb). Despite sustained virologic response at week 12 Sustained virologic response (SVR12) rates >95%, addiction centers in Italy are not allowed to prescribe direct‐acting antivirals (DAA). To increase testing and linkage to care a dedicated program including “ad hoc” transportation and fast‐track access to care was offered to PWUD from Puglia. Over 12 months, 1,470 individuals seen at 15 Services for Dependence (SERDs) underwent screening. For HCVAb positive, a fast‐track evaluation was offered at our Hepatology Unit. Patients were subsequently taken to their pharmacists to receive the prescribed DAA regimen. Treatment and adherence were supervised by SERDs physicians, SVR12 assessed at our unit. The scalability of the process was based on both, number of patients screened in our region in 2018, and number of PWUD diagnosed and treated at our center during 2018–2019. Of 1,470 individuals screened, 634 (43.1%) tested HCVAb positive. Overall, 231 were RNA positive, 54% of whom on opioid agonist therapy (OAT) and 32% with cirrhosis. Median interval between RNA assessment and treatment start was 22 days (0–300). Patients received 12‐week sofosbuvir/velpatasvir regimen without Ribavirin; in 220 patients who completed treatment, SVR12 was 98.6%. Among GT3, SVR12 was 98%. No re‐infection was observed. Improvements in screening, and linkage to care were registered. A PWUD‐tailored service led to HCV care cascade improvement and high SVR12 rates. Despite history of drug addiction, social instability and logistic barriers, micro‐elimination programs providing dedicated care are key drivers of success.

Electromagnetism, with its scalar charges, is based on an Abelian gauge theory, whereas non-Abelian gauge theories with vector charges describe strong and weak interactions, with a coupled spatial and charge (color) dynamics. New Abelian gauge fields have been synthesized artificially, allowing the study of extraordinary physical effects. The most well-known example is the Berry curvature, the cornerstone of topological physics. Synthetic non-Abelian gauge fields have been implemented only recently, but their action on the spatial dynamics of their emergent charges has not been studied experimentally so far. Here, by exploiting optically anisotropic 2D perovskite in the strong light–matter coupling regime, we experimentally synthesized a static non-Abelian gauge field, acting on an exciton-polariton quantum flow at room temperature. We observe experimentally the corresponding curved trajectories and spin precession. Our work could therefore open perspectives to study the non-Abelian physics using highly flexible photonic simulators.

Ground-penetrating radar (GPR) mapping provides a three-dimensional analysis of archaeological features within the context of landscape studies. The method’s ability to measure the intensity of radar reflections from deep in the ground can produce images and maps of buried features not visible on the surface. A study was conducted in some areas near the Domus Romana in Rabat (Malta) in order to investigate the still uncovered archaeological structures. The purpose of the GPR survey was to guide the excavation operations (planned but postponed due to Covid-19) and to allow us to understand the development of the defensive walls of the city and any other structures related to the Roman mansion. The choice of the areas to be investigated was therefore guided both by previous archaeological excavations and by the considerations made above. The results obtained through the GPR made it possible to shed light on some of the aspects related to the questions posed by the archaeologists, highlighting part of the structures related to the defensive walls, part of the structures related to water supply and conservation and part of the wall structures related to the Roman mansion itself.

•Efficacy of combinations vssunitinib remain debated in patients with favorable risk.•Favorable risk mRCC patients receiving TKIs as first-line therapy were enrolled.•One metastatic site correlated with longer OS in mRCC patients with good prognosis.•In patients with 1 metastatic site hepatic involvement resulted in worse PFS and OS.•The metastatic site should be considered in the therapeutic choice.