Search

AbstractThe aim of this work was to study the effects of red orange and lemon extract (RLE) inclusion on volatile organic compounds (VOCs) and sensory profile of lamb meat aged seven days. A total of 44 Merino lambs were randomly divided into two experimental groups: one that received the RLE (n = 22) and the control group (CON; n = 22). The RLE extract was orally and individually administered (90 mg/kg of live weight) to each lamb every day from colostrum assumption until slaughter (40 ± 1 days). Longissimus lumborummuscle was sampled and dry aged at 4 °C for seven days. The VOC and sensorial analyses were carried out at 1, 3 and 7 days. A total of 65 VOCs were detected. Aldehyde family was the most abundant, followed by ketones and alcohols in both groups. Extending ageing period, content of aldehydes and thiols increased only in control group (p < 0.01), but no differences were observed 24 h after slaughtering (p > 0.05). Regardless of dietary treatment, sensory evaluation, tenderness and juiciness showed a similar trend in both groups. Along ageing days, a significant improvement in these patterns was observed (p < 0.05). Our results showed that RLE inclusion did not have effects on both volatile compounds and sensory profile after slaughtering; ageing improves some sensory characteristics of lamb meat and the inclusion of RLE also seems to have a positive effect on the production of VOCs and on sensory properties such as meaty odour and overall liking.

•Most of the low-risk PeSCC have a good prognosis and would not deserve an adjuvant treatment.•Almost all relapses occur within 1 year (6 out of 7), and this arises the question of how plan surveillance, specifically addressing the early period with frequent examinations and visits.•Younger patients, considered the higher risk of relapse, may be placed in discussion for mini-invasive staging of lymph nodes, as an alternative to observation alone.

Los tumores malignos del tracto urinario están asociados a gran morbimortalidad siendo su prevalencia variable a nivel global. Recientemente el estudio IDENTIFY ha publicado resultados sobre la prevalencia del cáncer del tracto urinario a nivel internacional. Este estudio evalúa la prevalencia de cáncer dentro de la cohorte española del estudio IDENTIFY para determinar si los resultados publicados son extrapolables a nuestra población.

Prognostic tools in pathological-node (pN) patients after radical cystectomy (RC) are needed. To evaluate the prognostic impact of lymph node (LN)-density on disease-specific survival (DSS) in patients with bladder cancer (BC) undergoing RC with pelvic lymph node dissection. We analyzed a multi-institutional cohort of 1169 patients treated with upfront RC for cT1-4aN0M0 urothelial BCat nine centers. LN-densitywas calculated as the ratio of the number of positive LNs×100% to the number of LNs removed. The optimal LN-density cut-off value was defined by creating a time-dependent receiver operating characteristic (ROC) curve in pN patients. Univariable and multivariable Cox’ regression analyses were used to assess the effect of conventional Tumor Nodes Metastasis (TNM) nodal staging system, LN-density and other LN-related variables on DSS in the pN-positive cohort. Of the 1169 patients, 463 (39.6%) patients had LN-involvement. The area under the ROC curve was 0.60 and the cut-off for LN-density was set at 20%, 223 of the pN-positive patients (48.2%) had a LN-density.20%. In multivariable models, the number of LN-metastases (HR 1.03, p = 0.005) and LN-density, either as continuous (HR 1.01, p = 0.013) or as categorical variable (HR 1.37, p = 0.014), were independently associated with worse DSS, whereas pN-stage was not. LN-density.20% was an independent predictor of worse DSS in BC patients with LN-involvement at RC. The integration of LN-density and other LN-parameters rather than only conventional pN-stage may contribute to a more refined risk-stratification in BC patients with nodal involvement.

Background: The BONSAI phase II trial recently demonstrated the activity of cabozantinib in metastatic collecting duct patients. The outcomes of patients in this setting treated with immunotherapy as second-line is unknown. The aim of the present report was to describe outcomes of patients enrolled in the BONSAI trial that received nivolumab as second-line treatment.Material and methods: We describe the oncological outcomes in terms of overall response rate, progression-free survival, overall survival and safety. We excluded patients that did not receive any second-line treatment or were treated with agents other than nivolumab.Results: We identified five patients of whom one was excluded due to lack of data. Three patients obtained clinical benefit (one partial response, two stable disease); the second-line progression-free survival (nivolumab) ranged from 2.8 to 19.9 months to and second-line overall survival ranged from 5.1 to 26.5 months. No new safety signals were observed.Conclusions: Nivolumab may be considered as second-line therapy option after cabozantinib failure in selected metastatic collecting duct carcinoma patients.

Introduction: Fournier’s Gangrene (FG) has still a mortality rate up to 45%. Several studies identified prognostic factors but there is a knowledge gap concerning procalcitonin (PCT) levels and mortality risk in FG. This study is aimed to assess the role of PCT as prognostic factor in FG.Materials and methods: The medical records of 20 male FG patients admitted at the Department of Urology of “Cattinara” Hospital, University of Trieste between January 2019 and November 2020 were retrospectively reviewed. Clinical, demographic, microbiological data were collected. The Fournier’s Gangrene Severity Index (FGSI) was calculated for each patient.Results: Thirteen (65%) of 20 patients survived. Median age was 58 years (IQR 51–88), 15 patients (75%) had a Charlson Comorbidity Index (CCI) score ⩾2, 1 (5%) equal to 0, 4 to 1 (20%). Median FGSI score was 6 (IQR 2–12) and median PCT 0.8 ng/ml (IQR 0.04–2.12). At multivariate analysis PCT levels >0.05 ng/ml were associated with an increased overall mortality risk (OR 2.14, CI 1.25–4.27, p= 0.002). CCI score ⩾2 (OR 1.51, CI 1.01–2.59, p= 0.04), Streptococcical etiology (OR 3.41, CI 2.49–4.61, p= 0.002) and FGSI score >9 (OR 1.41, CI 1.19–2.21, p= 0.004) were associated with unfavorable outcome.Conclusion: PCT might be a prognostic factor in FG. CCI and FGSI are useful tools in mortality risk stratification. Streptococcical etiology is associated with unfavorable outcome. Further larger clinical trials are pending.

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 study aimed to evaluate quality of nephrolithometric nomograms to predict stone-free rates (SFRs) and complication rates (CRs) in case of minimally invasive percutaneous nephrolithotomy (PNL). In the last decade, nomograms have been introduced to estimate the SFRs and CRs of PNL. However, no data are available regarding their reliability in case of utilization of miniaturized devices. Herein we present a prospective multicentric study to evaluate reliability of Guy’s stone score (GSS), the stone size, tract length, obstruction, number of involved calyces, and essence of stone (S.T.O.N.E.) nephrolithometry score and Clinical Research Office of the Endourological Society (CROES) score in patients treated with minimally invasive PNL.

AbstractOxidative stress causes several pathological conditions in farm animals by inducing a reduction in animal welfare and production with major economic losses for livestock. The standardised phytoextract obtained by red orange and lemon processing has antioxidant and anti-inflammatory activities. In this study we have investigated whether treating lambs for 40 days with red orange and lemon extract (RLE) was able to prevent the antioxidant and anti-inflammatory mechanisms, typically in newborn period. For this purpose, at the end of treatment, redox status was assessed in plasma using oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Moreover, 8-hydroxy-2’-deoxyguanosine (8-OHdG) in urine was measured as a biomarker of DNA damage and finally, the markers of inflammatory status, interleukin (IL) 1β and 6, were measured in plasma by using an enzyme-linked immunosorbent assay (ELISA). Results showed that RLE-treated lambs improved antioxidant mechanisms as demonstrated by the increase in SOD, CAT and GPx activities and, furthermore, a significant reduction in oxidative stress-induced damage was demonstrated through MDA and 8-OHdG measurements. Moreover, RLE was also able to prevent the increase of pro-inflammatory cytokines concentration, such as IL- 1 β and IL 6. Results showed in the present paper demonstrate the potential beneficial effects of the RLE in lambs.HIGHLIGHTSOxidative stress causes economic loss and welfare impairment in livestock.Several oxidative markers can be used to assess the redox status in plasma.The activity of some antioxidant enzymes increased in RLE treated lambs.A reduction of pro-inflammatory cytokines was recorded in RLE treated lambs.

IMPORTANCE: Metastatic collecting duct carcinoma (mCDC) is a rare type of non–clear cell renal cell carcinoma (ncRCC) with poor prognosis and no standard treatments. Despite retrospective series that have documented the benefit of cabozantinib in ncRCC, no prospective trials have evaluated this treatment in mCDC. OBJECTIVE: To determine whether cabozantinib is an active treatment in patients with mCDC. DESIGN, SETTING, AND PARTICIPANTS: The caBozantinib in cOllectiNg ductS Renal Cell cArcInoma (BONSAI) trial was an open-label, single-arm, phase 2 clinical trial carried out between January 2018 and November 2020 at a single academic center with data cut off in September 2021 on behalf of the the Italian Network for Research in Urologic-Oncology (Meet-URO 2). Eligible patients had histologic diagnosis of centrally confirmed mCDC with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). In total, 25 patients were screened. INTERVENTIONS: Patients received cabozantinib, 60 mg orally once daily, until disease progression, unacceptable toxic effects, or withdrawal of consent. MAIN OUTCOMES AND MEASURES: The primary end point was objective response rate (ORR) per RECIST, version 1.1. RESULTS: At data cut off, of 25 patients enrolled, 23 started treatment because 2 were excluded after failing the screening process at pathologic review. The median follow-up cannot be estimated using the reverse Kaplan-Meier estimator. The median time to censoring was 11 months (95% CI, 0-22 months). Median (range) age was 66 (53-74) years. As best overall response, 3 patients presented stable disease, 1 patient achieved a complete response, and 7 a partial response. The ORR was 35% (95% CI, 16%-57%). The median progression-free survival was 4 months (95% CI, 3-13 months). The median OS was 7 months (95% CI, 3-31 months). All patients reported at least 1 grade (G) 1 to 2 adverse event (AE). The most common G1 to G2 AEs were fatigue (14 [60%]), anorexia (9 [39%]), hand-foot syndrome (7 [30%]), hypothyroidism (7 [30%]), mucositis (7 [30%]), diarrhea (5 [22%]), and hypertension (3 [13%]). Six G3 AEs were reported: 2 arterial hyperthension, 1 pulmonary thromboembolism, 1 bleeding, and 2 fatigue. There were no permanent discontinuations from the study owing to AEs. Four patients (17%) required dose reduction to 40 mg, and 4 (17%) required a transitory interruption to manage toxic effects. CONCLUSIONS AND RELEVANCE: The study met the ORR primary end point, showing encouraging efficacy of cabozantinib in untreated patients with mCDC. Further investigations to advance the molecular understanding of this tumor are ongoing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03354884

The occurrence of river floods is strongly related to specific climatic conditions that favor extreme precipitation events leading to catchment saturation. Although the impact of precipitation and temperature patterns on river flows is a well discussed topic in hydrology, few studies have focused on the relationship between peak discharges and standard Climate Change Indices (ETCCDI) of precipitation and temperature, widely used in climate research. It is of interest to evaluate whether these indices are relevant for characterizing and predicting floods in the Alpine area. In this study, a correlation analysis of the ETCCDI indices annual time series and annual maximum flows is presented for the Piedmont Region, in North-Western Italy. Spearman’s rank correlation is used to determine which ETCCDI indices are temporally correlated with maximum discharges, allowing to hypothesize which climate drivers better explain the interannual variability of floods. Moreover, the influence of climate (decadal) variability on the tendency of annual maximum discharges is examined by spatially correlating temporal trends of climate indices with temporal trends of the discharge series in the last twenty years, calculated using the Theil-Sen slope estimator. Results highlight that, while extreme precipitation indices are highly correlated with extreme discharges at the annual timescale, with different indices that are consistent with catchment size, the decadal tendencies of extreme discharges may be better explained by the decadal tendencies of the total annual precipitation over the study area. This suggests that future projections of the annual precipitation available from climate models simulations, whose reliability is higher compared to precipitation extremes, may be used as covariates for non-stationary flood frequency analysis.

•Penile squamous cell (PSCC) carcinoma is a rare tumor with an aggressive behavior.•Meet-URO 23/I-RARE database is a multicentric registry on rare genitourinary tumors.•This retrospective study evaluates clinical outcomes and prognostic factors in PSCC.•Patients with an ORR to I line platinum-based chemotherapy have a better survival.•Poor ECOG PS, lymph node metastases and higher age are poor prognostic factors.

The unprecedented challenges posed by the global COVID-19 pandemic have magnified the significance of managing intensive care patients in prone positions, particularly those requiring mechanical ventilation. Central venous access is crucial for delivering essential therapies to patients, particularly in intensive care settings. However, the shift in patient management during the pandemic, necessitating prone positioning for improved oxygenation, presented unique hurdles in maintaining and establishing central venous access. Before the pandemic, scant literature detailed the insertion of vascular access devices in prone or unconventional positions. Limited case reports and letters highlighted the feasibility of procedures like ultrasound-guided central catheter placement in patients undergoing surgery or with specific clinical needs. During the pandemic, a surge in case reports and series illuminated the complexities faced by clinicians in maintaining vascular access during pronation procedures. These reports delineated critical scenarios, ranging from rapid clinical deterioration necessitating immediate interventions to challenges with vascular access device (VAD) malfunctions or misplacements during prone maneuvers. Patient selection and device types emerged as critical considerations. Various scenarios, including patients transitioning to prone position from non-invasive ventilation and those requiring additional access for therapies like dialysis, posed challenges in device selection and placement. Successful VAD insertion techniques in prone patients encompassed multiple anatomical sites, including the internal jugular, brachial, femoral, and popliteal veins. However, challenges persisted, particularly with respect to anatomical variations and technical complexities in cannulation. Further research, standardized protocols, and randomized studies are needed to refine and validate the proposed strategies in both pandemic and non-pandemic settings.

AbstractIn this work we investigate the spatial variability of sub-daily rainfall extremes over Italy considering the influence of local orographic effects. We consider the average annual maxima computed from the recently-released Improved Italian – Rainfall Extreme Dataset (I2-RED) in about 3800 time series with at least 10 years of data (1916–2020 period) and we analyze the orographic effects through a local regression approach which gathers stations in a grid cell-centered area of 1 km resolution. Several constraints are considered to tackle problems determined by the low data density of some areas and by the extrapolation at low/high elevations. Different criteria for selecting the local sample are examined. This work confirms with increased detail previous findings, such as a generally positive gradient of the 24 h average annual maxima and the evidence of negative gradients in large mountainous areas for the 1 h maxima. The use of a local regression approach allows to identify the areas showing the reverse orographic effect, providing material for future investigations on the physical explanation of this evidence. Moreover, the reconstructed maps will allow to apply more accurate approaches in works related to the spatial variability of other rainfall statistics, such as the quantiles required for hydrologic design.