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41.
Disease control with prior platinum-based chemotherapy is prognostic for survival in patients with metastatic urothelial cancer treated with atezolizumab in real-world practice
Marina Mencinger, Dushan Mangaroski, Urška Bokal, 2021, original scientific article

Abstract: Background. Atezolizumab, a programmed-death ligand-1 (PD-L1) inhibitor, is a novel treatment option for patients with metastatic urothelial cancer (mUC). Clinical prognostic factors, survival outcomes, and the safety of patients with mUC treated with atezolizumab, in a real-world setting, were investigated.Patients and methods. 62 patients with mUC, treated at the Institute of Oncology Ljubljana between May 8th 2018 and Dec 31st 2019, were included. Response rates and immune-related adverse events (irAE) were collected. Progression-free survival and overall survival times were assessed using the Kaplan-Meier method. The Cox propor-tional hazards model was applied to identify the factors affecting survival. Results. Of 62 patients, five (8.1%) have not yet been evaluated and 20 (32%) died prior to the first radiographic evaluation. We observed clinical benefit in 19 (33%), objective response in 12 (21%), and complete response in five (9%) patients. Median overall survival for the whole population was 6.8 (95% CI, 2.6–11.0), for platinum-naïve 8.7 (95% CI: 0.8–16.5), and for the platinum-treated group 6.8 (95% CI, 3.7–10) months. At the 5.8 (0.3–23.1) month median follow-up, the median duration of the response was not reached. IrAE occurred in 20 (32%) patients and seven (11%) of them discontinued the treatment. Multivariate analysis in platinum-treated patients showed that a treatment-free interval of more than six months was prognostic for overall survival (OS). Conclusions. Responses to atezolizumab led to long disease remission in a subset of our patients. The median OS in our real-world population was compromised by a large percentage of patients with poor ECOG performance status (PS). A treatment-free interval from chemotherapy was associated with the longer survival of platinum-treated pa-tients with mUC receiving further atezolizumab.
Keywords: PD-L1 inhibitor, urothelial cancer, bladder, atezolizumab
Published in DiRROS: 23.07.2024; Views: 4; Downloads: 0
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42.
Clinical outcomes in stage III non-small cell lung cancer patients treated with durvalumab after sequential or concurrent platinum-based chemoradiotherapy : single institute experience
Martina Vrankar, Karmen Stanič, Staša Jelerčič, Eva Ćirić, Ana Lina Vodušek, Jasna But-Hadžić, 2021, original scientific article

Abstract: Chemoradiotherapy (ChT-RT) followed by 12-month durvalumab is the new standard treatment for unresectable stage III non-small cell lung cancer. Survival data for patients from everyday routine clinical practice is scarce, as well as potential impact on treatment efficacy of sequential or concomitant chemotherapy and the us-age of gemcitabine.Patients and methods. We retrospectively analysed unresectable stage III NSCLC patients who were treated with durvalumab after radical concurrent or sequential chemotherapy (ChT) from December 2017 and completed treat-ment until December 2020. We assessed progression free survival (PFS), overall survival (OS) and toxicity regarding baseline characteristic of patients.Results. Eighty-five patients with median age of 63 years of which 70.6% were male, 56.5% in stage IIIB and 58.8% with squamous cell carcinoma, were included in the analysis. Thirty-one patients received sequential ChT only, 51 patients received induction and concurrent ChT and 3 patients received concurrent ChT only. Seventy-nine patients (92.9%) received gemcitabine and cisplatin as induction chemotherapy and switched to etoposide and cisplatin during con-current treatment with radiotherapy (RT). Patients started durvalumab after a median of 57 days (range 12–99 days) from the end of the RT and were treated with the median of 10.8 (range 0.5–12 months) months. Forty-one patients (48.2%) completed treatment with planned 12-month therapy, 25 patients (29.4%) completed treatment early due to the toxicity and 16 patients (18.8%) due to the disease progression. Median PFS was 22.0 months, 12- and estimated 24-month PFS were 71% (95% CI: 61.2–80.8%) and 45.8% (95% CI: 32.7–58.9%). With the median follow-up time of 23 months (range 2–35 months), median OS has not been reached. Twelve- and estimated 24-month OS were 86.7% (95% CI: 79.5–93.9%) and 68.6% (95% CI: 57.2–79.9%).Conclusions. Our survival data are comparable with published research as well as with recently published real-world reports. Additionally, the regimen with gemcitabine and platinum-based chemotherapy as induction treatment was efficient and well tolerated.
Keywords: non-small cell lung cancer, stage III, chemoradiotherapy, durvalumab, acute toxicity
Published in DiRROS: 23.07.2024; Views: 4; Downloads: 2
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43.
Preoperative intensity-modulated chemoradiotherapy with simultaneous integrated boost in rectal cancer : five-year follow-up results of a phase II study
Jasna But-Hadžić, Anja Meden Boltežar, Tina Škerl, Vesna Zadnik, Vaneja Velenik, 2021, original scientific article

Abstract: We conducted a phase II study to investigate the feasibility and safety of preoperative radiochemo-therapy experimental fractionation, using intensity-modulated radiation therapy with simultaneous integrated boost (IMRT SIB) to shorten the overall treatment time without dose escalation in intermediate/locally advanced rectal cancer with the aim to improving treatment outcome.Patients and methods. A total of 51 patients with operable stage II–III rectal carcinoma were included between January 2014 and January 2015. Fifty patients completed preoperative IMRT treatment with an elective dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/T3 and 48.4 Gy to T4 tumour in 22 fractions, with concomitant capecit-abine (825 mg/m2/12 h, including at weekends). Median follow-up was 70 months (range 11–80 m).Results. Forty-seven patients completed treatment per protocol. Acute toxicity occurred in 2 (4%) patients. R0 resec-tion was achieved in all but 1 and pathologic complete response (pCR) in 12 (25.5%) patients who had 5-year overall survival (OS), disease-free survival (DFS) and local control (LC) of 91.7%, 100% and 100%, respectively. The intention-to-treat analysis showed that the type of surgery significantly moderated OS and DFS, while total downstaging and pN were predictive for DFS only. For treatment per protocol 5-year OS, DFS and LC were 80.9% (95% confidence interval [CI] 69.7–92.1), 77.1% (95% CI 65.1–89.1) and 95.2% (95% CI 88.7–100), respectively. The proportion of patients with severe late (CTCAE G ≥ 3) gastrointestinal, urinary and sexual toxicity was 15%, 2% and 8% respectively, with one reported secondary carcinoma.
Keywords: rectal cancer, IMRT, simultaneous integrated boost, preoperative radiochemotherapy, acute toxicity
Published in DiRROS: 23.07.2024; Views: 5; Downloads: 3
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44.
Bridging biotremology and chemical ecology : a new terminology
Valerio Mazzoni, Gianfranco Anfora, Reginald Bifield Cocroft, Fatouros Nina E., Meta Virant-Doberlet, 2024, review article

Abstract: Living organisms use both chemical and mechanical stimuli to survive in their environment. Substrate-borne vibrations play a significant role in mediating behaviors in animals and inducing physiological responses in plants, leading to the emergence of the discipline of biotremology. Biotremology is experiencing rapid growth both in fundamental research and in applications like pest control, drawing attention from diverse audiences. As parallels with concepts and approaches in chemical ecology emerge, there is a pressing need for a shared standardized vocabulary in the area of overlap for mutual understanding. In this article, we propose an updated set of terms in biotremology rooted in chemical ecology, using the suffix ‘-done’ derived from the classic Greek word ‘δονέω’ (pronounced ‘doneo’), meaning ‘to shake’.
Keywords: vibrational communication, chemical ecology, biotremology, semiophysicals, pherodones, allelodones, zoology
Published in DiRROS: 23.07.2024; Views: 5; Downloads: 5
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45.
Scaphoideus titanus forecasting and management : quo vadis?
Elena Gonella, Giovanni Benelli, Nathalie Arricau-Bouvery, Domenico Bosco, Meta Virant-Doberlet, 2024, review article

Abstract: Scaphoideus titanus Ball (Hemiptera: Cicadellidae) is a major pest for European viticulture due to its high efficiency in the transmission of one of the most destructive pathogens for grapevine, namely flavescence dorée phytoplasmas. Although it plays a major role in spreading this disease, S. titanus is part of a complex epidemiological cycle involving several alternative vectors with variable relevance for phytoplasma spread. Here we provide an updated review on S. titanus monitoring and modelling, as well as the available tools for management of this pest and for limiting phytoplasma transmission and, thus, also spread. Insecticide-based control is examined; additional emphasis is placed on innovative and low-impact control approaches, such as vibrational mating disruption, biocontrol, and methods to reduce vector competence. We also discuss the main emerging challenges to the implementation of effective and sustainable control programs against S. titanus.
Keywords: epidemiology, pest monitoring, modelling, Integrated Pest Management, vibrational mating disruption, biological control, plant resistance elicitors, RNA-interference, symbiotic control, entomology, insects, plant protection
Published in DiRROS: 23.07.2024; Views: 9; Downloads: 5
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46.
Scaphoideus titanus up-to-the-minute : biology, ecology, and role as a vector
Elena Gonella, Giovanni Benelli, Nathalie Arricau-Bouvery, Domenico Bosco, Meta Virant-Doberlet, 2024, review article

Abstract: Native to the Nearctic region, Scaphoideus titanus Ball (Hemiptera: Cicadellidae) has become a major threat for grapevine production after being unintentionally introduced into Europe, where it became the main vector of flavescence dorée phytoplasma, being mainly associated with the genus Vitis. Scaphoideus titanus is a highly efficient vector of the most important phytoplasma affecting grapevine. For this reason, compulsory insecticide treatments have been introduced against this pest in many European countries. Moreover, the continuous expansion of its geographical distribution makes this leafhopper a serious threat for several non-European Countries. In this article, we review the current knowledge about its taxonomy, morphology, biology, ecology, and its role as a vector. Finally, we point out the main challenges for research aimed at reducing S. titanus and flavescence dorée expansion across Europe and avoiding spread of the disease outside the Old World.
Keywords: vector distribution, life cycle, morphology, taxonomy, feeding behaviour, entomology, insects
Published in DiRROS: 23.07.2024; Views: 9; Downloads: 3
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47.
Harmonizing microstructures and enhancing mechanical resilience : novel powder metallurgy approach for Zn–Mg alloys
Anna Boukalová, Jiří Kubásek, David Nečas, Peter Minárik, Črtomir Donik, Drahomír Dvorský, Dalibor Vojtěch, Alena Michalcová, Matjaž Godec, Irena Paulin, 2024, original scientific article

Abstract: Zinc alloys are recognised for their excellent biocompatibility and favourable corrosion rates, making them suitable for bioabsorbable implants. However, their mechanical properties necessitate improvement to fulfil the rigorous requirements of biomedical applications. This research focuses on engineering pseudo-harmonic structures within zinc alloys through a comprehensive method combining mechanical alloying, spark plasma sintering, and hot extrusion techniques. This fabrication process results in a composite material characterised by a soft core surrounded by a continuous, three-dimensional, ultrafine-grained hard shell. The experiment involved blending pure zinc with Zn–1Mg alloy powder, leading to the formation of both ductile zinc and fine-grained Zn–1Mg regions. While the Mg2Zn11 intermetallic phase was found to enhance the alloy's mechanical strength, the presence of oxide shells adversely affected the material's properties. The elimination of these shells via hot extrusion markedly improved the alloy's tensile strength, reaching an average value of tensile strength of 333 ± 7 MPa. This study provides significant insights into the material engineering of zinc-based alloys for biodegradable implant applications, demonstrating a viable approach to optimising their mechanical performance.
Keywords: zinc, magnesium, biodegradable, powder metallurgy, harmonic structure
Published in DiRROS: 23.07.2024; Views: 22; Downloads: 7
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48.
Microstructural, corrosion and mechanical properties of a WE43 alloy : conventional extrusion versus SPD
Anna Dobkowska, Aleksandra Zielińska, Irena Paulin, Črtomir Donik, Milena Koralnik, Bogusława Adamczyk-Cieślak, Monika Wieczorek-Czarnocka, Dariusz Kuc, Jiří Kubásek, Tomasz Mikuszewski, Matjaž Godec, Jarosław Mizera, 2024, original scientific article

Abstract: A hexagonal close-packed-structure WE43 alloy was extruded without any preheating of the initial billet using extrusion with an oscillating die to improve the corrosion and mechanical properties. The WE43 alloy was extruded at high ratios of R 1 5:1, R 2 7:1 and R 3 10:1. Electron back-scatter diffraction and transmission electron microscopy were used to determine the microstructural properties of the alloys. The influence of the extrusion method and the extrusion ratios on the corrosion and mechanical properties were investigated. Electrochemical tests were performed, and the corrosion damage was inspected. Tensile tests were made using micro specimens. When compared to conventional extrusion, the microstructural changes obtained with the KoBo method at R 5:1 increased the corrosion resistance, which was not only due to the grain refinement, but also due to the intensity of the texture. A decline in the corrosion resistance of the alloys deformed at higher extrusion ratios was observed. This was a result of the massive plastic strain imposed by the KoBo die. The room-temperature mechanical properties of the KoBo-extruded alloys were improved. However, at higher temperatures the mechanical properties decreased due to the solutioning of tiny triple precipitates.
Keywords: WE43, several plastic deformation, microstructure, corrosion, mechanical properties
Published in DiRROS: 23.07.2024; Views: 8; Downloads: 2
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49.
Exploring the microstructure, mechanical properties, and corrosion resistance of innovative bioabsorbable Zn-Mg-(Si) alloys fabricated via powder metallurgy techniques
David Nečas, Vojtěch Hybášek, Jan Pinc, Andrea Školáková, Ilona Voňavková, Klára Hosová, Martin Zlámal, Anna Boukalová, Jan Pokorný, Drahomír Dvorský, Črtomir Donik, Dalibor Vojtěch, Jiří Kubásek, 2024, original scientific article

Abstract: Zinc alloys belong to the widely studied materials for applications like medical devices, however, they often encounter an inappropriate combination of mechanical/corrosion/biological properties. In this respect, we produced the Zn–1Mg and Zn–1Mg–1Si containing biologically friendly elements with potential strengthening effects on zinc matrix by powder metallurgy methods including mechanical alloying, spark plasma sintering, and extrusion further enabling the formation of materials with unique extremely fine-grained microstructures. The systematic study of these materials showed the possibility of reaching homogeneous nano-grain microstructure and high strength values exceeding 450 MPa in tension. Selected chemical composition and processing methods led also to slightly decreased wear and corrosion rates and rather uniform corrosion.
Keywords: zinc, mechanical alloying, biodegradable metals, composite, spark plasma sintering, extrusion, powder metallurgy
Published in DiRROS: 23.07.2024; Views: 16; Downloads: 5
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50.
Diagnostic performance of p16/Ki-67 dual immunostaining at different number of positive cells in cervical smears in women referred for colposcopy
Uršula Salobir Gajšek, Andraž Dovnik, Iztok Takač, Urška Ivanuš, Tine Jerman, Simona Šramek Zatler, Alenka Repše-Fokter, 2021, original scientific article

Abstract: . The aim of the study was to evaluate the diagnostic accuracy of p16/Ki-67 dual immunostaining (p16/ Ki-67 DS) in cervical cytology and the number of positive p16/Ki-67 cells to diagnose high grade cervical intraepithelial neoplasia (CIN2+) in colposcopy population. Subjects and methods. We performed an analysis on a subset cohort of 174 women enrolled within a large-scale randomised controlled human papillomavirus (HPV) self-sampling project organised as part of the population-based Cervical Cancer Screening Programme ZORA in Slovenia. This subset cohort of patients was invited to the colposcopy clinic, underwent p16/Ki-67 DS cervical cytology and had the number of p16/Ki-67 positive cells determined. Results. Among analysed women, 42/174 (24.1%) had histologically confirmed CIN2+. The risk for CIN2+ was increasing with the number of positive cells (p < 0.001). The sensitivity of p16/Ki-67 DS for detection of CIN2+ was 88.1%, specificity was 65.2%, positive predictive value was 44.6% and negative predictive value was 94.5%. Conclusions. Dual p16/Ki-67 immunostaining for the detection of CIN2+ has shown high sensitivity and high negative predictive value in our study, which is comparable to available published data. The number of p16/Ki-67 positive cells was significantly associated with the probability of CIN2+ detection. We observed a statistically significant and clinically relevant increase in specificity if the cut-off for a positive test was shifted from one cell to three cells.
Keywords: cervical cytology, high-grade dysplasia, p16/Ki-67 immunostaining
Published in DiRROS: 22.07.2024; Views: 35; Downloads: 5
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