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Abstract Background Anti-PD-(L)1 agent are approved as first- and second-line treatment options in advanced urothelial cancer (UC), but information about long-term survival is scarce. There is a need for prognostic factors, as these may help in the decision-making concerning anti-PD-(L)1 in patients with UC. Here, we examined long-term survival following anti-PD-(L)1 in advanced UC and assessed clinical factors for their correlation with survival. Methods We collected data from patients with advanced UC treated with anti-PD-(L)1 between 2013 and 2023. Overall- and progression-free survival (OS, PFS) were determined using the Kaplan-Meier method. Independent variables were analysed by uni- and multivariate Cox regression for their association with OS and PFS. Results Survival analyses included 552 patients. Patient characteristics in our cohort were consistent with those of a typical advanced UC population. After median follow-up of 49 months, five-year OS and PFS rates were 16.0% and 6.9% respectively. The absence of visceral and/or bone metastases and elevated C-reactive protein level, gamma-glutamyltransferase level and neutrophil-to-lymphocyte ratio were identified as favourable prognostic factors for OS. Conclusions A selected subset of patients with advanced UC may experience long-term clinical benefit from anti-PD-(L)1 treatment. We identified prognostic factors that might be used for risk assessment and clinical trial stratification.

Durante los últimos años, hasta finales de 2023, se experimentó una extraordinaria disminución en los caudales del Río Paraná y por ende en el Río de la Plata. Este fenómeno se destacó tanto por su intensidad como por su prolongada duración, adquiriendo características históricas. El presente estudio se desarrolló en el contexto de este episodio, con el objetivo de evaluar si el descenso de caudal pudiera provocar un avance del frente salino hacia el interior del Río de la Plata y eventualmente afectar la captación de las plantas potabilizadoras de la costa argentina. Para abordar esta cuestión se empleó modelación matemática, considerando diversos escenarios hidrometeorológicos y condiciones de borde. Los resultados obtenidos indican que, incluso en estas condiciones adversas, la calidad de las tomas de agua cruda no se vería comprometida por incrementos en la salinidad. Esta conclusión se respalda, al menos parcialmente, mediante mediciones de conductividad eléctrica realizadas en puntos del Río de la Plata cercanos a las tomas.

Octogenarian patients with diffuse large B-cell lymphoma are managed mainly with palliation, but recent improvement in their overall condition makes potentially curative treatment a possibility. Studies have shown that half of selected octogenarians may be cured using reduced-dose anthracycline chemoimmunotherapy. However, patients aged >85 (late octogenarians [LO]) were underrepresented, and selection criteria were poorly defined. We analyzed the clinical characteristics and outcomes of LO enrolled in the FIL Elderly Project in terms of the treatment received (palliative vs. curative) and of their simplified geriatric assessment (sGA), then compared them with early octogenarians (EO) aged 80- 84 and with those aged 65-79 classified as UNFIT or FRAIL according to sGA enrolled in the same study. Of the 1,163 patients, 370 were >80 and 129 LO. Clinical characteristics were similar between LO and EO, but LO more frequently received palliation (50% vs. 23%; P=0.001) and had worse 2-year overall survival (OS) (48% vs. 63%; P=0.001) and 2-year progression-free survival (PFS) (43% vs. 56%; P=0.01). Patients receiving anthracycline did better than patients receiving palliation (P

Abstract Background Diffusion‐weighted whole‐body MRI (DW‐MRI) is increasingly used in the management of multiple myeloma (MM) patients, but data regarding the prognostic role of DW‐MRI imaging response after treatment are lacking. The Myeloma Response Assessment and Diagnosis System (MY‐RADS) imaging recommendations recently proposed the criteria for response assessment category (RAC) with a 5‐point scale in order to standardize response assessment after therapy, but this score still needs to be validated. Methods We investigated the prognostic role of RAC criteria in 64 newly diagnosed MM patients after autologous stem cell transplantation (ASCT), and we combined the results of MY‐RADS with those of minimal residual disease (MRD) assessment by multiparametric flow cytometry (MFC). Results Superior post‐ASCT PFS and OS were observed in patients with complete imaging response (RAC1), with respect to patients with imaging residual disease (RAC≥2): median PFS not reached (NR) versus 26.5 months, p = 0.0047, HR 0.28 (95% CI: 0.12–0.68); 3‐year post‐ASCT OS 92% versus 69% for RAC1 versus RAC ≥2, respectively, p = 0.047, HR 0.24 (95% CI: 0.06–0.99). Combining MRD and imaging improved prediction of outcome, with double‐negative and double‐positive features defining groups with excellent and dismal PFS, respectively (PFS NR vs. 10.6 months); p = 0.001, HR 0.07 (95%CI: 0.01–0.36). Conclusion The present study supports the applicability of MY‐RADS recommendations after ASCT; RAC criteria were able to independently stratify patients and to better predict their prognosis and the combined use of DW‐MRI with MFC allowed a more precise evaluation of MRD.

MYC translocations, a hallmark of Burkitt lymphoma, occur in 5-15% of diffuse large B-cell lymphoma, and have a negative prognostic impact. Numerical aberrations of MYC have also been detected in these patients, but their incidence and prognostic role are still controversial. We analyzed the clinical impact of MYC increased copy number on 385 patients with diffuse large B-cell lymphoma screened at diagnosis for MYC, BCL2, and BCL6 rearrangements. We enumerated the number of MYC copies, defining as amplified those cases with an uncountable number of extra-copies. The prevalence of MYC translocation, increased copy number and amplification was 8.8%, 15%, and 1%, respectively. Patients with 3 or 4 gene copies, accounting for more than 60% of patients with MYC copy number changes, had a more favorable outcome compared to patients with >4 copies or translocation of MYC, and were not influenced by the type of treatment received as first-line. Stratification according to the number of MYC extra-copies showed a negative correlation between an increasing number of copies and survival. Patients with >7 copies or the amplification of MYC had the poorest prognosis. Patients with >4 copies of MYC showed a similar, trending towards worse prognosis compared to patients with MYC translocation. The survival of patients with >4 copies, translocation or amplification of MYC seemed to be superior if intensive treatments were used. Our study underlines the importance of fluorescence in situ hybridization testing at diagnosis of diffuse large B-cell lymphoma to detect the rather frequent and clinically significant numerical aberrations of MYC.

Antonia Pierobon,1 Elisa Sini Bottelli,1 Laura Ranzini,1 Claudio Bruschi,2 Roberto Maestri,3 Giorgio Bertolotti,4 Marinella Sommaruga,5 Valeria Torlaschi,1 Simona Callegari,1 Anna Giardini1 1Psychology Unit, 2Department of Pulmonary Rehabilitation, 3Department of Biomedical Engineering, Istituti Clinici Scientifici Maugeri, IRCCS, Montescano, 4Psychology Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Tratate, 5Clinical Psychology and Social Support Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Camaldoli, Italy Abstract: In addition to clinical comorbidities, psychological and neuropsychological problems are frequent in COPD and may affect pulmonary rehabilitation delivery and outcome. The aims of the study were to describe a COPD population in a rehabilitative setting as regards the patients depressive symptoms, anxiety, mild cognitive impairment (MCI) and self-reported adherence and to analyze their relationships; to compare the COPD sample MCI scores with normative data; and to investigate which factors might predict adherence to prescribed physical exercise. This was a multicenter observational cross-sectional study. Of the 117 eligible stable COPD inpatients, 84 were enrolled according to Global initiative for chronic Obstructive Lung Disease (GOLD) criteria (mainly in Stage III–IV). The assessment included Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), anxiety, depression and self-reported pharmacological and nonpharmacological adherence. From the MMSE, 3.6% of patients were found to be impaired, whereas from the MoCA 9.5% had a likely MCI. Patients referred had mild-severe depression (46.7%), anxiety (40.5%), good pharmacological adherence (80.3%) and difficulties in following prescribed diet (24.1%) and exercise (51.8%); they struggled with disease acceptance (30.9%) and disease limitations acceptance (28.6%). Most of them received good family (89%) or social (53%) support. Nonpharmacological adherence, depression, anxiety and MCI showed significant relations with 6-minute walking test, body mass index (BMI) and GOLD. Depression was related to autonomous long-term oxygen therapy modifications, disease perception, family support and MCI. In the multivariate logistic regression analysis, higher BMI, higher depression and lower anxiety predicted lower adherence to exercise prescriptions (P=0.0004, odds ratio =0.796, 95% CI =0.701, 0.903; P=0.009, odds ratio =0.356, 95% CI =0.165, 0.770; and P=0.05, odds ratio =2.361, 95% CI =0.995, 5.627 respectively). In COPD patients, focusing on pharmacological and nonpharmacological adherence enhance the possibility of tailored pulmonary rehabilitation programs. Keywords: depression, anxiety, mild cognitive impairment, adherence, COPD, pulmonary rehabilitation

Objective: Ovarian hyper-stimulation during IVF is associated with a significant raise in serum estrogens and one may expect detrimental effects on estrogen-dependent diseases such as endometriosis. However, available evidence from large case series of affected women performing IVF is generally reassuring with the possible exception of women carrying deep invasive lesions. On this basis we deemed important investigating more in depth whether women with deep invasive endometriosis could be a subgroup at higher risk of recurrence or disease progression during IVF. Study design: Women with endometriosis who underwent IVF and who had a second evaluation after 3–6 months from a failed cycle were retrospectively reviewed. The main inclusion criteria were the presence of deep invasive endometriosis and/or a history of surgery for this form of the disease. The primary aim of the study was to determine the frequency of endometriosis-related complications in the interval between the two evaluations. Secondary aims were pain symptoms and lesion size modifications. Results: Eighty-four women were ultimately selected: baseline ultrasound documented deep invasive lesions in 60 of them. One case of possible endometriosis-related complication was recorded, corresponding to a rate of 1.2% (95%: 0.05%–5.5%) for the whole cohort and 1.7% (95%CI: 0.08–7.6%) for the subgroup of women with ultrasound detected lesions. This rate appears similar to the reported frequency of endometriosis progression in women not receiving IVF. No significant modifications in pain symptoms or lesions size occurred. Conclusions: Women with deep invasive endometriosis who underwent IVF do not seem to be exposed to a substantially increased risk of recurrence/disease progression. Larger evidence from independent groups is however required for a definitive conclusion. Keywords: Deep invasive endometriosis, IVF, Recurrence

INTRODUCTION:Chronic obstructive pulmonary disease (COPD) is a complex multi-component disorder characterized by progressive irreversible respiratory symptoms and extrapulmonary comorbidities, including anxiety-depression and mild cognitive impairment (MCI). However, the prevalence of these impairments is still uncertain, due to non-optimal screening methods. This observational cross-sectional multicentre study aimed to evaluate the prevalence of anxiety-depressive symptoms and MCI in COPD patients, identify the most appropriate cognitive tests to screen MCI, and investigate specific cognitive deficits in these patients and possible predictive factors. MATERIALS AND METHODS:Sixty-five stable COPD inpatients (n = 65, aged 69.9±7.6 years, mainly stage III-IV GOLD) underwent the following assessments: Hospital Anxiety and Depression Scale (HADS), Geriatric Depression Scale (GDS) or Beck Depression Inventory-II (BDI-II), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a complete neuropsychological battery (ENB-2) including different cognitive domains (attention, memory, executive functions, and perceptive and praxis abilities). RESULTS:Moderate-severe anxiety was present in 18.5% of patients and depressive symptoms in 30.7%. The prevalence of MCI varied according to the test: 6.2% (MMSE), 18.5% (MoCA) and 50.8% (ENB-2). In ENB-2, patients performed significantly worse compared to Italian normative data on digit span (5.11±0.9 vs. 5.52±1.0, p = 0.0004), trail making test-B (TMT-B) (176.31±99.5 vs. 135.93±58.0, p = 0.004), overlapping pictures (26.03±8.9 vs. 28.75±8.2, p = 0.018) and copy drawing (1.370.6 vs. 1.61±0.5, p = 0.002). At logistic regression analysis, only COPD severity (p = 0.012, odds ratio, OR, 4.4 [95% CI: 1.4-14.0]) and anxiety symptoms (p = 0.026, OR 4.6 [1.2-17.7]) were significant and independent predictors of the deficit in copy drawing, which assesses visuospatial and praxis skills. CONCLUSION:Given the prevalence of neuropsychological impairments in COPD patients, the routine adoption in rehabilitation of screening tools for mood and cognitive function, including digit span, TMT-B and copy drawing, may be useful to detect psychosocial comorbidities and personalize the rehabilitative program.

In this study, Cabernet Sauvignon and Chardonnay musts, and fruit juices from cherry, kiwi, peach, and strawberry were co-fermented with Saccharomyces cerevisiae EC1118 and Torulaspora delbrueckii UMY196 at two different proportions (80:20 (v/v) and 60:40 (v/v)). The most pleasant fruit-based drink was obtained with Cabernet Sauvignon must and kiwi juice in a proportion of 60:40 and fermented with T. delbrueckii. This beverage was produced in higher volume to simulate a scale-up, and the aromatic profile, sensory description, and consumer acceptability were determined. The most powerful odorants of the kiwi-based drink were ethyl octanoate, phenylethanal, ethyl hexanoate, vinyl-guaiacol, benzaldehyde, and nonanal, for which the odor activity values were 21.1, 3.3, 2.6, 2.2, 1.9, and 1.6, respectively. These findings were in accordance with the sensory analysis, since the emerged descriptors were fruity (ethyl octanoate), honey and floral (phenylethanal), apple and peach (ethyl hexanoate), and citrus (nonanal). The consumers judged the kiwi-based drink acceptable (67%) and 39% of them would buy it. The reliable fermentation of a grape must/fruit juice was demonstrated. The kiwi-based drink represents an innovative and pleasant beverage with a positive impact on sustainability as its production can limit the loss of fresh fruits, as well as contribute to the enological field.

Objectives: To report on the early detection of congenital heart disease (CHD) in low‐ and high‐risk populations managed at our hospital; and perform a detailed analysis of false‐negative diagnoses, in order to derive possible recommendations on how to reduce their incidence. Methods: This was a retrospective observational study analyzing cases which underwent an ultrasound examination at the end of the first trimester at the Fetal Medicine and Surgery Unit of Gaslini Children's Hospital, Genoa, Italy, in the period January 2015 to December 2021. The study population included both low‐risk pregnancies that underwent standard first‐trimester combined screening and high‐risk ones referred to our unit because of a positive combined test or suspicion of fetal anomalies raised in a regional community hospital. For each case, the following variables were retrieved and analyzed: number of fetuses, maternal body mass index, gestational age at first‐trimester screening, whether the pregnancy was low or high risk, nuchal translucency thickness (normal or > 99th centile), type of CHD, associated extracardiac anomalies, karyotype and pregnancy outcome. For low‐risk pregnancies, suspicion of CHD was also recorded. In low‐risk cases, sonographic cardiac screening comprised evaluation of the four‐chamber view (grayscale and color/power Doppler) and three‐vessel‐and‐trachea view (color/power Doppler). High‐risk cases underwent early fetal echocardiography. False‐negative cases were categorized according to likely cause of the missed diagnosis, as follows: human factor; technical factor; acoustic‐window factor. Results: Gestational age at ultrasound ranged from 12 + 0 to 13 + 6 weeks (crown–rump length (CRL), 50.1–84.0 mm) in the low‐risk group and from 11 + 5 to 13 + 6 weeks (CRL, 45.1–84.0 mm) in the high‐risk group. Over the 7‐year study period, 7080 pregnancies were evaluated in the first trimester. Of these, 6879 (7167 fetuses) were low‐risk and 201 were high‐risk cases. In the low‐risk group, there were 30 fetuses with CHD (including 15 major and 15 minor CHD), yielding a prevalence of 4.2/1000 (2.1/1000 for major CHD). Nine of the 30 CHD cases were suspected at screening ultrasound (7/15 major CHD). Excluding cases in which the CHD would not be expected to be associated with a modification of the screening views and would therefore not be detectable on screening ultrasound, 7/12 cases of major CHD were detected, corresponding to a sensitivity of 58.3%. Among the 201 high‐risk cases, there were 46 fetuses with CHD (including 44 major and two minor CHD), of which 43 were detected, corresponding to a sensitivity for early fetal echocardiography of 93.5%, or 97.7% if the two cases that were unlikely to be detectable on first‐trimester screening were excluded. Analysis of the 11 (of 24) false‐negative cases that would be expected to be picked up on screening views revealed that human error (image interpretation and/or scanning approach) was involved in all 11 cases and technical factors (excessive color priority (color‐balance function) and/or incorrect plane alignment) were present in two. There was impairment of the acoustic window (associated with maternal obesity and/or twin gestation) as a cofactor in five of the 11 cases. Conclusions: The sensitivity for detection of major CHD of early cardiac screening in low‐risk pregnancy is under 60%, partly due to the natural history of CHD and, it seems, partly relating to human error and technical issues with image quality. Factors associated with false‐negative diagnoses may be categorized into three types: human error, technical factors and acoustic‐window impairment. We recommend: appropriate assessment with fetal posterior spine; that sufficient time is spent on assessment of the fetal situs; and that color/power Doppler settings are adapted to the individual case. A lower threshold for referring doubtful cases for early fetal echocardiography should be adopted in cases of maternal obesity and in twin gestation. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]