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Patients with head and neck squamous cell carcinoma (HNSCC) who have progressed following primary treatment (PT) have a poor prognosis. In this group, nivolumab has been demonstrated to significantly improve outcomes. This study presents the efficacy of nivolumab in Polish patients with recurrent and/or metastatic (R/M) HNSCC using real-world data. The analyzed group consisted of 324 adult patients with R/M HNSCC following platinum-based therapy. Patients were divided into 3 groups based on the time from completion of PT to nivolumab initiation (tPT-N): within 6 months (refractory), between 6 and 24 months (sensitive, tPT-N ≤24), and beyond 24 months (sensitive, tPT-N >24). Survival analysis and the Cox proportional hazards model were performed to evaluate how various risk factors affect patient outcomes. The 1-year and 2-year overall survival (OS) was 19.1%, 6.1%, 30.7%, 9.4%, and 45.7%, 29.1% in refractory, sensitive tPT-N ≤24, sensitive tPT-N >24 patients, respectively and was higher for both sensitivity groups vs. refractory (p = .004) and for sensitive tPT-N >24 versus refractory and sensitive tPT-N ≤24 (p <.001). Patients with nasopharyngeal cancer had OS significantly higher than patients with other primary tumor localization. The multivariate Cox analysis showed a significant favorable effect of tPT-N >24 (HR = 0.53, p = .001) and nasopharyngeal cancer on OS (HR = 0.20, p = .008). Conversely, female sex was identified as an unfavorable factor for OS (HR = 1.48, p = .020). In our study, we established that the benefit of nivolumab increases with the increasing tPT-N. The probability of death is significantly lower in male patients and patients with nasopharyngeal cancer regardless of tPT-N., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: The IN-PATSAT32 and QLQ-INFO25 are questionnaires which can be applied to assess and improve communication with cancer patients, as well as for research and clinical trials aimed at assessing patients' satisfaction and perception of the information received from nurses and other healthcare providers. Given the recently passed "Polish oncological network" act of law, the issue of patient satisfaction and its regular assessment is finally acknowledged in the socioeconomic and cultural context of Poland. The aim of this study was to validate the EORTC quality of information, QLQ-INFO25, and satisfaction with care, IN-PATSAT32 modules., Methods: This prospective cross-sectional study included patients from a cancer reference center in Krakow, Poland. The translated and pilot-tested module QLQ-INFO25 was used together with the core questionnaire QLQ-C30 and the satisfaction module IN-PATSAT32. Adult patients with histological confirmation of any malignancy and the ability to answer the questionnaire were included in the study., Results: A total of 187 patients, including 111 women and 76 men (mean age ± SD; 59.32 ± 10.4), were enrolled. The Cronbach's alpha coefficients, ranged from 0.83-0.85 for the QLQ-INFO25 and 0.82-0.94 for the IN-PATSAT32, indicating positive internal consistency. Acceptable convergent and discriminant validity in multi-trait scaling analyses was observed for both modules, with r < 0.3 for all calculations. Interclass correlations proved satisfactory test-retest reliability., Conclusions: The Polish versions of the IN-PATSAT32 and QLQ-INFO25 are reliable and valid instruments providing domains not covered by the core EORTC module. These tools are suitable for use in daily clinical practice, in research as well as in clinical trials to obtain data regarding patients' perception of and satisfaction with received information within the socioeconomic and cultural context of Poland., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Jagiellonian University Collegium Medicum Bioethics Committee (registry KBET/253/B/2011). Informed consent was obtained from all the participants. The study followed the Declaration of Helsinki with its amendments. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Immune checkpoint inhibitors have improved the treatment of metastatic renal cell carcinoma (RCC), with the combination of nivolumab (NIVO) and ipilimumab (IPI) showing promising results. However, not all patients benefit from these therapies, emphasizing the need for reliable, easily assessable biomarkers. This multicenter study involved 116 advanced RCC patients treated with NIVO + IPI across nine oncology centers in Poland. Blood markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), eosinophils, and monocytes were assessed at baseline, after three months, and before disease progression (PD). The prognostic significance of these parameters was analyzed using linear regression, Kaplan-Meier survival analysis, and Cox regression models. After a median follow-up of 11.8 months, the progression-free survival (PFS) was 12.8 months (95% confidence interval [CI] 5.7-28.1), while the overall survival (OS) was 27.3 months (95% CI 16-not reached). Patients with an NLR increase of ≥ 25% had a PFS of 8.2 (3.1-24.7) months compared to 17.5 (8.6-28.1) months in those with a rise in < 25% (p = 0.015). Similarly, a ≥ 25% increase in PLR was linked to a PFS of 6.8 (2.8-8.3) months compared to 17.4 (8.4-28.1) months (p < 0.001). Multivariate analysis confirmed PLR as an independent predictor of PFS (HR 2.9, 95% CI 1.5-5.6, p = 0.001), while elevated eosinophil levels were associated with a reduced risk of death (HR 0.2, 95% CI 0.04-0.9, p = 0.05). No other analysis was statistically significant. NLR, PLR, and eosinophil levels may serve as valuable biomarkers for predicting treatment response in RCC patients receiving NIVO + IPI., Competing Interests: Declarations. Competing interests: RPM has received travel grants from Accord, BMS, MSD, and lecture fees from Astra Zeneca, BMS, GSK, Novartis, Roche, MSD; AD has received travel grants and lecture fees from Roche, BMS, Janssen, Molteni, MSD, Accord; AGW has received travel grants and lecture fees from Roche, Novaris, Lili, Astellas, Pfizer, Amgen, Swixx, Pierre Fabre, Egis, BMS, MSD; JC has received lecture fees from BMS; NVV has no financial interests; DTM has received travel grants and lecture fees from MSD, Pierre Fabre, BMS, Novartis, Pfizer; JD has received travel grants and lecture fees from Amgen, AstraZeneca, BMS, MSD, Novartis, Nutricia; AR has received travel grants and lecture fees from Roche, BMS, Ipsen, Pfizer, Novartis, Gilead, MSD; AB has received travel grants and lecture fees from BMS, MSD, Astellas, Merck, Servier, Astra Zeneca, Pfizer; MS has received travel grants and lecture fees from Roche, BMS, Janssen, MSD, Amgen, Astellas., Ipsen, Pfizer, Novartis, Gilead; AGU has received travel grants from GSK, Lilly, Astra Zeneca, Gilead, Accord, and lecture fees from Astra Zeneca. JW has no financial interests; PB has received travel grants, lecture fees, and advisory boards from AstraZeneca, MSD, GSK, Pharma; ŁS has received travel grants from BMS, Accord; MP has received travel grants and lecture fees from AstraZeneca, Roche, Novartis, Elli Lilly, Janssen, Gilead, and Amgen. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Jagiellonian University Medical College (approval number 118.0043.1.115.2024, dated April 19, 2024). Consent to participate: Informed, institutional consent was obtained from all individual participants included in the study before starting treatment., (© 2025. The Author(s).)

The common iliac arteries (CIA) are the main finals branches of the abdominal aorta. The aim of the present meta-analysis was to demonstrate the most up-to-date and evidence-based data regarding the general anatomy of the CIAs, including their length, take-off angles, and diameters. PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar were searched to find all studies considering the anatomy of the CIA. Eligibility assessment and data extraction stages were performed. The results of the measurements in a total of 5785 patients were evaluated and included in the statistical analysis. The prevalence of the origin variations of the CIA has been evaluated. CIA was found to most commonly originate at the level of L4 vertebrae with a pooled prevalence of 59.49% (95% CI 48.00-70.50%). The overall mean length of the CIA was 5.59 mm (SE: 0.13), and the mean diameter of the CIA was 10.52 mm (SE: 0.85). The knowledge of the anatomy and variations of the CIA is crucial in lumbar spine surgery, especially when performing the anterolateral approach to L4 and L5 vertebrae. Furthermore, the level of the aortic bifurcation has significant implications related to vascular surgery in this region. We performed the present meta-analysis to standardize the extensive information on the anatomy of the CIAs., Competing Interests: Declarations. Conflict of interest: The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024. The Author(s).)

Introduction: Sacituzumab govitecan (SG) is approved for patients with previously treated metastatic or locally advanced triple-negative breast cancer (TNBC), as per the ASCENT trial results. Real-world studies (RWSs) cover more diverse patients than clinical trials, offering crucial data for healthcare policies. This study aimed to investigate the safety and efficacy of SG in real-world Polish patients with previously treated metastatic TNBC., Methods: In this ambispective multicenter cohort study, we collected demographic and clinical data. Premedication, adjustments in SG dosage, and treatment regimen adhered to the product's characteristics., Results: We included 79 female patients. The median age at SG initiation was 53 years; 32% of patients were initially diagnosed with a non-TNBC subtype. The median number of previous palliative lines was 2. Seven patients presented with brain metastases. The median overall survival was 10.3 months, and the median progression-free survival (PFS) was 4.4 months. The overall response rate was 35%, with a median time to response of 2 months. SG was discontinued by 70% of patients, primarily due to disease progression (95%). Treatment delays due to adverse events (AEs) occurred in 67% and dose reductions in 25% of patients, with neutropenia being the most common. Grade ≥ 2 AEs included neutropenia (43%), anemia (10.1%), and diarrhea (4%). A longer interval between breast cancer diagnosis and SG initiation or between metastasis diagnosis and SG initiation correlated with improved PFS, likely reflecting the disease's biological aggressiveness rather than treatment efficacy., Conclusion: In this RWS, SG demonstrated effectiveness and safety in patients with previously treated metastatic TNBC, consistent with ASCENT trial outcomes. Further research is needed to explore the efficacy of SG in different patient populations and healthcare systems., Competing Interests: Declarations Conflict of Interest Miroslawa Püsküllüoğlu obtained travel grants and lecture honoraria from AstraZeneca, Roche, Novartis, Elli Lilly, Janssen, Gilead and Amgen; Małgorzata Pieniążek travel grants and lecture fees from Pfizer and Novartis; lecture fees from Gilead, advisory board from Novartis; Manuela Las-Jankowska, Joanna Streb and Paulina Kilian-Van Miegem report no conflicts of interest. Marek Ziobro reports travel grants and lecture honoraria from Pierre Fabre, Novartis, Ipsen; Renata Pacholczak-Madej travel grants from Accord, GSK, BMS, lecture fees from BMS; Agnieszka Rudzińska from Gilead, BMS, Sandoz; Aleksandra Grela-Wojewoda from Novartis, BMS, Pierre Fabre, Roche, Amgen, MSD, Gilead and Pfizer, Aleksandra Łacko from Astra Zeneca, Pfizer, Novartis, Eli Lilly, Roche, Gilead Science including advisory board member role; Michał Jarząb conference fees by Gilead, Roche, speaker’s honoraria by Novartis, Roche, Lilly, Pfizer, Teva, Exact Sciences, Mammotome, advisory boards by Novartis, Pfizer; and Anna Polakiewicz-Gilowska lecture honoraria and travel grants from AstraZeneca, Roche, Novartis, Elli Lilly, Swixx, Gilead and Pfizer. Ethical Approval All activities conducted in studies involving human participants adhered to the ethical guidelines set forth by the institutional ethical committee and were in accordance with the principles outlined in the 1964 Helsinki Declaration and its subsequent amendments or equivalent ethical standards. This study was approved by the Ethical Committees of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw Branch, Poland (reference number 21/2024, dated 22 Feb 2024) and Krakow Branch (reference number 2/2023 dated 18 April 2023). Informed consent, including standard institutional consent, was obtained from each patient before initiating SG treatment under the national reimbursement program. The Ethical Committee determined that informed consent for retrospective data collection was not required., (© 2024. The Author(s).)

Background: Immune checkpoint inhibitors (ICIs) have been employed in the adjuvant and metastatic setting of renal cell carcinoma (RCC) treatment. Among ICIs, combined immunotherapy has the highest risk for immune-related adverse events (irAEs). We aimed to document the incidence of irAEs in RCC patients treated with nivolumab and ipilimumab as data from the European population remain limited., Materials and Methods: We analysed data from 88 RCC patients treated with nivolumab + ipilimumab between May 2022 and June 2024 across six high-volume oncology units in Poland. We reviewed irAEs and estimated their impact on survival parameters via univariate and multivariate Cox proportional hazards regression models, along with log-rank tests., Results: With a median follow-up of 11.3 months, the median overall survival (OS) was not reached, whereas the median progression-free survival (PFS) was 12.8 months (6.3-19.3). A total of 74 irAEs were recorded in 50 patients. The most frequent events were endocrine (n = 20, 27%), hepatic (n = 15, 17%), general (n = 12, 13.6%), and cutaneous (n = 11, 12.5%). The occurrence of irAEs was associated with a 60% lower risk of disease progression (hazard ratio 0.44, 95% confidence interval 0.2-0.87, p = 0.018) without impacting OS and higher disease control rate (n = 45, 90% vs. n = 24, 63.2%, p = 0.004). In contrast, patients with hepatotoxicity had poorer outcomes, with a 2.6-fold greater risk of death (p = 0.05)., Conclusions: IrAEs may serve as a predictive factor for the efficacy of the nivolumab + ipilimumab regimen in RCC patients. Special attention is needed for hepatotoxicity, as it can significantly impact survival outcomes., Competing Interests: Declarations Competing interests RPM travel grants from Accord, BMS, MSD, lecture fees from BMS, GSK, Novartis, Roche; AD travel grants and lecture fees from Roche, BMS, Janssen, Molteni, MSD, Accord; ŁS travel grants from BMS, Accord; AD travel grants and lecture fees from BMS, MSD, Astellas, Merck, Servier, Astra Zeneca, Pfizer; JD travel grants and lecture fees from Amgen, AstraZeneca, BMS, MSD, Novartis, Nutricia; AGW travel grants and lecture fees from Roche, Novaris, Lili, Astellas, Pfizer, Amgen, Swixx, Pierre Fabre, Egis, BMS, MSD; AR travel grants and lecture fees from Roche, BMS, Ipsen, Pfizer, Novartis, Gilead, MSD; DTM travel grants and lecture fees from MSD, Pierre Fabre, BMS, Novartis, Pfizer; JW no declared; PB travel grants, lecture fees, and advisory boards from AstraZeneca, MSD, GSK, Pharma; MP travel grants and lecture fees from AstraZeneca, Roche, Novartis, Elli Lilly, Janssen, Gilead and Amgen; Ethical approval The study protocol was approved by the Bioethics Committee of Jagiellonian University Medical College (decision number 118.0043.1.115.2024 dated April 19, 2024). Informed consent Standard institutional informed consent was obtained from each patient before initiating the nivolumab + ipilimumab treatment. Consent for publication Not applicable., (© 2024. The Author(s).)

Background : Palliative care must be tailored for patients with extended disease trajectories, such as those with hormone receptor-positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced breast cancer (ABC), including the appropriate timing of discontinuing treatment. This study aimed to assess the interval between the last oncologist visit and death and the application of systemic treatment near the end of life in this patient population. Methods : This retrospective study included patients with luminal ABC who received at least two lines of palliative systemic treatment at the National Research Institute of Oncology in Poland, and died between November 2020 and March 2024. Results : Seventy-six women, with a median age 62.8 years (range: 35.3-91.5), were included. The median number of prior palliative systemic treatment lines was three (range: 2-6). At their last recorded oncologist visit, 75% of the patients were receiving active treatment (53% with hormonal therapy and 22% with chemotherapy). Only 25% were under continuous palliative care at this visit. Treatment was administered within the last month of life to 53% of the patients. The median duration from the last oncologist visit to death was 23 days (range: 0-408). The duration of this time interval was only associated with the performance status at the last visit ( p < 0.05). Conclusions : Oncologists frequently delay the recognition of the need to discontinue systemic therapy. Patients with luminal HER2-negative ABC may be offered numerous effective lines of systemic treatment, complicating this decision further. Implementing clearer guidelines for end-of-life care for this group and providing proper training for healthcare providers is essential.

Randomized clinical trials demonstrated a recurrence-free survival benefit with adjuvant anti-programmed death-1 (anti-PD1) inhibitors of resected stage IIB-IV melanoma. However, no improvement in overall survival has been observed thus far. Furthermore, there are no predictive markers for immunotherapy response in melanoma, therefore adjuvant treatment is offered to all comers based exclusively on the pathological and clinical stages. Additionally, one year of treatment duration and the risk of chronic immune-related adverse effects may negatively impact patients´ quality of life. In this review, we will try to answer whether the currently available data on adjuvant anti-PD1 therapy of stage IIB-IV resected melanoma is sufficient to make this strategy available to all patients. We will also discuss the economic impact of this therapy on healthcare system budgets. Recent studies suggest that the high cost of cancer drugs may affect access to these agents globally by raising questions of sustainability for patients and society., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SO received honoraria and travel grants from: Bristol Myers Squibb, MSD, Pierre Fabre, Novartis, and Roche. MP received honoraria from: Roche, Eli Lilly, Novartis, Pierre Fabre, Astra Zeneca, Gilead, and Janssen. RPM received honoraria and travel grants from: Bristol Myers Squibb, MSD, and Roche. ORM declares no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a variable clinical manifestation, potentially leading to death. Importantly, patients with SLE have an increased risk of neoplastic disorders. Thus, this study aimed to comprehensively evaluate the clinical and laboratory characteristics of patients with SLE and with or without malignancy., Methods: We conducted a retrospective analysis of medical records of 932 adult Caucasian patients with SLE treated at the University Hospital in Kraków, Poland, from 2012 to 2022. We collected demographic, clinical, and laboratory characteristics, but also treatment modalities with disease outcomes., Results: Among 932 patients with SLE, malignancy was documented in 92 (9.87%), with 7 (7.61%) patients experiencing more than one such complication. Non-hematologic malignancies were more prevalent (n = 77, 83.7%) than hematologic malignancies (n = 15, 16.3%). Patients with SLE and malignancy had a higher mean age of SLE onset and a longer mean disease duration than patients without malignancy (p < 0.001 and p = 0.027, respectively). The former group also presented more frequently with weight loss (odds ratio [OR] = 2.62, 95% confidence interval [CI] 1.61-4.23, p < 0.001), fatigue/weakness (OR = 2.10, 95% CI 1.22-3.77, p = 0.005), and fever (OR = 1.68, 95% CI 1.06-2.69, p = 0.024). In the malignancy-associated group, we noticed a higher prevalence of some clinical manifestations, such as pulmonary hypertension (OR = 3.47, 95% CI 1.30-8.42, p = 0.007), lung involvement (OR = 2.64, 95% CI 1.35-4.92, p = 0.003) with pleural effusion (OR = 2.39, 95% CI 1.43-3.94, p < 0.001), and anemia (OR = 2.24, 95% CI 1.29-4.38, p = 0.006). Moreover, the patients with SLE and malignancy more frequently had internal comorbidities, including peripheral arterial obliterans disease (OR = 3.89, 95% CI 1.86-7.75, p < 0.001), myocardial infarction (OR = 3.08, 95% CI 1.41-6.30, p = 0.003), heart failure (OR = 2.94, 95% CI 1.30-6.17, p = 0.005), diabetes mellitus (OR = 2.15, 95% CI 1.14-3.91, p = 0.011), hypothyroidism (OR = 2.08, 95% CI 1.29-3.34, p = 0.002), arterial hypertension (OR = 1.97, 95% CI 1.23-3.23, p = 0.003), and hypercholesterolemia (OR = 1.87, 95% CI 1.18-3.00, p = 0.006). Patients with SLE and malignancy were treated more often with aggressive immunosuppressive therapies, including cyclophosphamide (OR = 2.07, 95% CI 1.30-3.28, p = 0.002), however median cumulative cyclophosphamide dose in malignancy-associated SLE subgroup was 0 g (0-2 g). Interestingly, over a median follow-up period of 14 years (ranges: 8-22 years) a total of 47 patients with SLE died, with 16 cases (5.28%) in the malignancy-associated SLE group and 31 cases (5.73%) in the non-malignancy SLE group (p = 0.76). The most common causes of death were infections (21.28%) and SLE exacerbation (8.51%)., Conclusion: The study highlights the relatively frequent presence of malignancies in patients with SLE, a phenomenon that demands oncological vigilance, especially in patients with a severe clinical course and comorbidities, to improve long-term outcomes in these patients., (© 2024. The Author(s).)

Introduction: Hepatic visceral crisis (VC), characterized by a rapid total bilirubin increase with disease progression, poses a life-threatening risk in advanced breast cancer (ABC). International consensus guidelines define VC and touch on impending VC (IVC). Limited data exist on systemic treatments for hepatic VC/IVC. This study explores the safety and efficacy of cisplatin monotherapy in patients with Human Epidermal Growth Factor Receptor 2- negative breast cancer (BC) and hepatic IVC/VC., Methods: In this retrospective single-center cohort study data of patients treated with cisplatin monotherapy (60-80 mg/m 2 , every 3-4 weeks) between 2016 and 2023 at a reference Cancer Centre in Southern Poland were analyzed., Results: 33 female patients (24/33 hormonal-positive) with the mean age 53.84 years were included. Participants progressed on median 2 prior palliative systemic treatment lines. In 10/23 patients hepatic VC and in 23/33 IVC (rapid, symptomatic liver progression; extensive liver involvement; alanine or aspartate aminotransferase > 2 × normal limit; significant increases in lactate dehydrogenase, alkaline phosphatase, or gamma-glutamyl transferase) were identified. Median progression-free survival was 1.87 months and median overall survival 2.67 months. 33% of the patients presented stable disease or partial response. Eight patients experienced adverse events grade ≥ 3: in five the dose of cisplatin was reduced; two stopped the treatment., Conclusion: Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are scarce. Our study explored cisplatin's potential use, finding it to be a viable option in patients with performance status 0 or 1 experiencing hepatic IVC/VC, irrespective of liver function parameters and other factors., (© 2024. The Author(s).)

Background and Purpose: Metaplastic breast carcinoma (BC-Mp) is an uncommon subtype that poses unique challenges. The limited information on patient prognosis and therapeutic strategies motivated our research initiative. We aimed to assess disease-free survival (DFS), overall survival (OS), and influential factors in patients with nonmetastatic BC-Mp., Materials and Methods: In this multicenter retrospective cohort study, clinicopathological data for nonmetastatic BC-Mp patients treated at four oncology units in Poland (2012-2022) were gathered., Results: Among 115 women (median age 61, range: 28-91), the median tumor size was 40 mm (range 20-130); 30% of patients exhibited positive local lymph nodes. The majority of patients presented with stage II (46%) and triple-negative breast cancer (TNBC) (84%). Radiotherapy was administered to 61% of patients. Surgical procedures included breast-conserving surgery in 31% of patients and mastectomy in 68%. Eighty-three per cent of patients received chemotherapy. The median estimated DFS and OS were 59 and 68 months, respectively. Multivariable analysis revealed that tumor size influenced DFS and OS (Hazard ratios [HR] = 1.02, 95%CI 0.01-0.03 for both endpoints) and taxanes application improved DFS (HR = 0.47, 95%CI 0.24-0.93), but other factors did not. For patients receiving neoadjuvant systemic therapy (N = 51), taxanes improved DFS and OS according to univariable analysis., Interpretation: Our findings highlight poor DFS and OS regardless of receiving optimal treatment, emphasizing the need for tailored therapeutic strategies for BC-Mp patients. Taxanes appear promising in a neoadjuvant setting, particularly within the current standard of care for the TNBC subtype.

Introduction: The advent of immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the management of mismatch repair deficient (MMR-d)/microsatellite instability-high (MSI-H) endometrial cancer (EC). Initially investigated as monotherapy in phase I-II clinical trials for recurrent disease, immunotherapy demonstrated remarkable activity, yielding overall response rates (ORR) ranging from 27% to 58%. Based on these promising findings, phase III trials have explored the integration of immunotherapy into first-line treatment regimens for advanced/recurrent EC in combination with chemotherapy or other agents such as tyrosine kinase inhibitors (TKIs), resulting in improved ORR, progression-free survival, and overall survival compared to the standard chemotherapy regimen of paclitaxel and carboplatin. As a result, the incorporation of ICIs with standard platinum-based chemotherapy is becoming a new standard of care in MMR-d/MSI-H EC., Areas Covered: This review synthesizes literature from PubMed, Embase databases, and recent congress abstracts on gynecological cancers. It covers MMR-d/MSI-H EC incidence, molecular diagnostics, clinical trial outcomes, predictive biomarkers for ICIs, patient profiles likely to benefit, resistance mechanisms, and the future of immunotherapy in this setting., Expert Opinion: By offering a comprehensive overview, this review delineates the pivotal role of ICIs in the management of MMR-d/MSI-H EC.

Cultural ecosystem services (CES) and disservices shape landscape planning policy to a huge extent. We focus on the benefits and disbenefits associated with CES. The study aimed to explore the co-occurrence of the benefits and disbenefits associated with CES as well as the relationship between spatial and landscape characteristics and specific benefits and disbenefits. We conducted a map-based online questionnaire among visitors of two urban green spaces in Kraków, Poland (Wolski Forest and Jordan Park). Respondents were asked to map places visited and assign them benefits and disbenefits using indicator statements. We found three bundles of benefits (connection to nature, social bonding in nature and responsibility) and five to seven bundles of disbenefits (1). The experiences (e.g., strengthening social bonds) were more concentrated whereas the identities (e.g., reflection) were more blurred spatially owing to their individualistic nature (2). The relationship between benefits/disbenefits and landscape features showed a relatively weak correlation, with a more discernible pattern observed in the case of experiences and capabilities (3). Respondents perceived more human-related disbenefits (overcrowding, noise, rubbish), exhibiting a greater geographical concentration, especially in proximity to tourist attractions (4). The ecosystem-related disbenefits (insects, allergies) were less geographically concentrated (5). Furthermore, the study unveiled differences in the perception of disbenefits across seasons. Visitors of warmer months expressed concerns about overcrowding, insects, and allergies, while those exploring the study areas in winter indicated challenges associated with darkness and snow-covered paths (6). These are important implications for management to increase the comfort of visits to green spaces., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Agnieszka Nowak-Olejnik reports financial support was provided by European Union. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Primary neuroendocrine neoplasms of the breast (Br-NENs) are rare. The classification has been updated in recent years making interpretation of the data published challenging. It is unclear whether neuroendocrine differentiation is associated with poorer prognosis and what treatment approaches should be applied., Methods: The database for breast cancer patients treated between 2009 and 2022 at the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow was explored to search for Br-NENs. Patients' medical and pathological data were collected and analyzed., Results: We included 22 females with Br-NEN without metastases at the time of diagnosis. The median age was 64 years (range: 28-88), Of the cases, 18 were hormone receptor positive, all were HER-2 negative, the median Ki67 was 27% (10-100%). The median tumor size at the time of diagnosis was 29.5mm (7-75mm), 9 patients were N-positive. DCIS was present in 5 cases. Only one case was negative for chromogranin and synaptophysin staining, but data were missing for 4 cases. Nine patients received adjuvant chemotherapy, mainly based on anthracyclines and taxanes, while 16 received adjuvant hormonal therapy and 15 received postoperative radiotherapy. Radical surgery was performed in all patients, but two underwent suboptimal tumorectomy. One patient had local recurrence, three experienced metastatic disease, all involving the lungs, but these patients are still alive. The median follow-up was 96 months (8-153). Two patients died, with a follow up time of no recurrence >4 years. Our results were compared to twelve case series collecting clinical data on Br-NENs, with median patient number of 10.5 (range: 3-142)., Conclusion: Br-NENs represent a heterogenous group of diseases, lacking data from prospective studies or clinical trials. There are no established treatment standards tailored for Br-NENs. Our patients' cohort exhibited a favorable prognosis, potentially attributed to lower tumor stage and Ki67 index compared to other reported case series. We suggest that radical surgery and postoperative radiotherapy be administered akin to standard treatment for breast cancer of no special type. ESMO also advocates for this approach in systemic treatment, although we recommend considering platinum-based chemotherapy for patients with poorly differentiated Br-NENs exhibiting high Ki67., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Püsküllüoğlu, Grela-Wojewoda, Ambicka, Pacholczak-Madej, Pietruszka, Mucha-Małecka, Rudzińska, Ziobro, Ryś and Mituś.)

Metaplastic breast cancer (BC-Mp), which includes a range of epithelial and mixed epithelial-mesenchymal tumours, are rare malignancies with an unfavourable prognosis. The limited literature on BC-Mp focuses mainly on retrospective data for radically treated patients. Notably absent are studies dedicated to the palliative treatment of BC-Mp with distant metastases. The present retrospective study investigated treatment modalities and prognosis in a multi-centre cohort of 31 female participants diagnosed with distant metastatic BC-Mp, including 7 patients with de novo metastatic disease. The median age of the patients was 61 years (range, 33-87 years), with 38.7% presenting local lymph node involvement. Lungs were the most common site for the metastatic disease (61.3%). Median Ki-67 index was 50% (range, 35-70%), and 80.7% of cases were classified as grade 3. Human epidermal growth factor receptor 2 (HER2) + and estrogen receptor + were detected in 12.9 and 6.5% of cases, respectively. A total of 62.4% of patients received first-line palliative systemic treatment. The 1- and 2-year overall survival (OS) were 38.5 and 19.2%, respectively. Receiving ≥1 line of palliative treatment was significantly associated with improved OS (P<0.001). Factors such as age, Ki-67 index, HER2 or hormonal status, presence of specific epithelial or mesenchymal components, location of metastases or chemotherapy regimen type did not influence OS. The present study provided insights into the clinicopathological profile, systemic treatment experience, prognostic factors and OS data of BC-Mp with distant metastases, emphasizing the imperative for clinical trials in this population., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Püsküllüoğlu et al.)

Recent reports have demonstrated that endothelial injury is critical in the pathogenesis of systemic sclerosis (SSc) and is associated with increased levels of circulating inflammatory biomarkers. This study aims to analyze the serum concentrations of selected cytokines and evaluate their relationship with SSc clinics and the long-term course of the disease. This study included 43 SSc patients and 24 matched healthy controls. In both groups, we measured serum levels of inflammatory cytokines related to the inflammatory response, such as tumor necrosis factor (TNF)α, interferon (IFN)γ, interleukin (IL)-4, IL-6, IL-10, and IL-17, and fibroblast activation protein (FAP). Additionally, in SSc patients, we evaluated the presence of four single nucleotide polymorphisms (SNPs) located in the promotor region of the TNFA gene, namely rs361525, rs1800629, rs1799964, and rs1799724, which might be related to increased TNFα concentrations. The main aim consisted of associating inflammatory cytokines with (1) clinical disease characteristics and (2) longitudinal observation of survival and cancer prevalence. SSc patients were characterized by a 17% increase in serum TNFα. There was no other difference in serum cytokines between the studied groups and diffuse vs. limited SSc patients. As expected, evaluated serum cytokines correlated with inflammatory biomarkers (e.g., IL-6 and C-reactive protein). Interestingly, patients with higher IL-17 had decreased left ventricle ejection fraction. During the median 5-year follow-up, we recorded four cases of neoplastic diseases (lung cancer in two cases, squamous cell carcinoma of unknown origin, and breast cancer with concomitant multiple myeloma) and nine deaths. The causes of death included lung cancer (n = 2), renal crisis (n = 1), multiple-organ failure (n = 1), and unknown reasons in five cases. Surprisingly, higher TNFα was associated with an increased cancer prevalence, while elevated IL-17 with death risk in the follow-up. Furthermore, the AG rs361525 genotype referred to higher TNFα levels than GG carriers. Both AG rs361525 and CT rs1799964 genotypes were associated with increased cancer risk. Higher serum concentrations of TNFα characterize the SSc patients, with the highest values associated with cancer. On the other hand, increased IL-17 in peripheral blood might predict poor SSc prognosis. Further research is needed to validate these findings., (© 2023. The Author(s).)

Metaplastic breast cancer (BC-Mp) presents diagnostic and therapeutic complexities, with scant literature available. Correct assessment of tumor size by ultrasound (US) and full-field digital mammography (FFDM) is crucial for treatment planning., Methods: A retrospective cohort study was conducted on databases encompassing records of BC patients (2012-2022) at the National Research Institutes of Oncology (Warsaw, Gliwice and Krakow Branches). Inclusion criteria comprised confirmed diagnosis in postsurgical pathology reports with tumor size details (pT) and availability of tumor size from preoperative US and/or FFDM. Patients subjected to neoadjuvant systemic treatment were excluded. Demographics and clinicopathological data were gathered., Results: Forty-five females were included. A total of 86.7% were triple-negative. The median age was 66 years (range: 33-89). The median pT was 41.63 mm (6-130), and eight patients were N-positive. Median tumor size assessed by US and FFDM was 31.81 mm (9-100) and 34.14 mm (0-120), respectively. Neither technique demonstrated superiority ( p > 0.05), but they both underestimated the tumor size ( p = 0.002 for US and p = 0.018 for FFDM). Smaller tumors (pT1-2) were statistically more accurately assessed by any technique ( p < 0.001). Only pT correlated with overall survival., Conclusion: The risk of underestimation in tumor size assessment with US and FFDM has to be taken into consideration while planning surgical procedures for BC-Mp.

Antibody drug conjugates (ADCs) comprise a rapidly growing class of targeted drugs that selectively deliver a cytotoxic agent to cancer cells, reducing the side effects associated with conventional chemotherapy. Breast cancer (BC) is a heterogeneous entity. The need for effective therapies for HER-2 negative BCs with poor prognosis, such as triple-negative or endocrine-resistant BC, remains unmet due to the lack of potential targets for treatments. These BC subtypes are not candidates for hormonal or anti-HER-2 agents. However, ongoing clinical trials exploring the use of ADCs with a wide range of targets have shown potential for this treatment modality. In this review, we present the current state of knowledge regarding the role of ADC and speculate on novel approaches including ADC combination therapies, new molecular targets, and the role of other subclasses of ADCs (bicycle drug conjugates, bispecific ADCs, immune modulating ADCs) in this clinical scenario., Competing Interests: Declaration of Competing Interest AR declares no conflict of interest. MP declares lectures fee or travel reimbursement from Amgen, AstraZeneca, Gilead, Janssen, Pfizer and Roche. RPM declares lectures fee or travel reimbursement from Roche, BMS, MSD, Novartis, Pfizer and Merck., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In cancer, immune checkpoint inhibitors (ICIs) improve patient survival but may lead to severe immune-related adverse events (irAEs). Rheumatic irAEs are a distinct entity that are much more common in a real-life than in clinical trial reports due to their unspecific symptoms and them being a rare cause of hospitalization. This review focuses on an interdisciplinary approach to the management of rheumatic irAEs, including cooperation between oncologists, rheumatologists, and immunologists. We discuss the immunological background of rheumatic irAEs, as well as their unique clinical characteristics, differentiation from other irAEs, and treatment strategies. Importantly, steroids are not the basis of therapy, and nonsteroidal anti-inflammatory drugs should be administered in the front line with other antirheumatic agents. We also address whether patients with pre-existing rheumatic autoimmune diseases can receive ICIs and how antirheumatic agents can interfere with ICIs. Interestingly, there is a preclinical rationale for combining ICIs with immunosuppressants, particularly tumor necrosis factor α and interleukin 6 inhibitors. Regardless of the data, the mainstay in managing irAEs is interdisciplinary cooperation between oncologists and other medical specialties.

Testing and vaccination have been major components of the strategy for combating the ongoing COVID-19 pandemic. In this study, we have developed a quantitative anti-SARS-CoV-2 spike (S1) IgG antibody assay using a fingerstick dried blood sample. We evaluated the feasibility of using this high-throughput and quantitative anti-SARS-CoV-2 spike (S1) IgG antibody testing assay in vaccinated individuals. Fingerstick blood samples were collected and analyzed from 137 volunteers before and after receiving the Moderna or Pfizer mRNA vaccine. Anti-SARS-CoV-2 S1 IgG antibody could not be detected within the first 7 days after receiving the first vaccine dose, however, the assay reliably detected antibodies from day 14 onwards. In addition, no anti-SARS-CoV-2 nucleocapsid (N) protein IgG antibody was detected in any of the vaccinated or healthy participants, indicating that the anti-SARS-CoV-2 S1 IgG assay is specific for the mRNA vaccine-induced antibodies. The S1 IgG levels detected in fingerstick samples correlated with the levels found in venous blood plasma samples and with the efficacy of venous blood plasma samples in the plaque reduction neutralization test (PRNT). The assay displayed a limit of quantification (LOQ) of 0.59 μg/mL and was found to be linear in the range of 0.51-1000 μg/mL. Finally, its clinical performance displayed a Positive Percent Agreement (PPA) of 100% (95% CI: 0.89-1.00) and a Negative Percent Agreement (NPA) of 100% (95% CI: 0.93-1.00). In summary, the assay described here represents a sensitive, precise, accurate, and simple method for the quantitative detection and monitoring of post-vaccination anti-SARS-CoV-2 spike IgG responses.

Nivolumab and ipilimumab combination became the first-line standard in advanced melanoma. We assessed its efficacy in a real-life study in Poland. In a one-year follow-up, we evaluated the medical records of 50 melanoma patients treated with that modality in five oncology centers. We recorded therapy outcomes and adverse events (AEs) after 3 and 12 months of therapy. At the first checkpoint, the disease control rate (DCR) was recorded in 58% (n = 29) of patients, but the same number of patients (n = 29, 58%) stopped immunotherapy due to disease progression (PD, n = 14, 48.3%), toxicity (n = 11, 37.9%) or death (n = 4, 13.8%). Among patients with DCR after the induction phase, 8 (27.6%) terminated due to toxicity, and 21 (72.4%) continued. However, at the 12-month checkpoint, only 14 patients (27% of all) were still receiving immunotherapy. In 7 (33.3%) it was discontinued due to PD (n = 2), toxicity (n = 2, 28.6% each), or death (n = 3, 42.9%). AEs occurred in 66.7% (n = 34) of patients; severe (grade 3 or 4) in half of them. Interestingly, those with AEs had an 80% lower risk of death (hazard ratio [HR] 0.2, 95% confidence interval [CI] 0.07−0.57, p = 0.001) and PD (HR 0.2, 95%CI 0.09−0.47, p < 0.0001). In the entire group of patients, after a 12-month follow-up, the median overall survival was not reached (NR, range: 6.8 months-NR) and progression-free survival was 6.3 (range: 3-NR) months. Our results demonstrate that combined immunotherapy is less effective in real-life than in pivotal trials. However, early responders will likely continue the therapy after a one-year follow-up. AEs occurrence might be a predictor of clinical effectiveness.

Purpose: Dermatomyositis and polymyositis (DM/PM) are rare autoimmune inflammatory myopathies, characterized by an increased risk of cardiovascular and thromboembolic events, likely related to the prothrombotic plasma properties. The aim of this study was to assess the in vitro thrombin generation profile as a biomarker of plasma procoagulant properties in DM/PM patients., Methods: In 58 clinically stable DM/PM patients and 67 controls matched for sex, age, body mass index, we measured plasma thrombin generation potential using the Calibrated Automated Thrombinography (CAT) and analyzed its relationship with clinical disease characteristics, including autoantibodies profile., Results: Patients with DM/PM had a 21% increase in endogenous thrombin potential (ETP), 36% higher peak thrombin concentration, and 11% faster thrombin generation, compared to controls (p ​< ​0.001, all, also after adjustment for potential confounders). Interestingly, although both diseases did not differ in thrombin generation potential, heterogenous variables predicted elevated ETPs in both of them. In DM, that was higher fibrinogen, C-reactive protein, and total cholesterol, whereas in PM, presence of arthritis and increased blood platelet count. Surprisingly, thrombin formation capacity remained in a robust inverse relationship with serum troponin (r ​= ​-0.67, p ​< ​0.001) in the patient group., Conclusions: DM/PM patients are characterized by an increased thrombin generation potential, suggesting prothrombotic plasma properties in both diseases. However, more studies are needed to verify its rationale and role in DM/PM clinical course and unfavorable clinical outcomes., (Copyright © 2022 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Trastuzumab-induced cardiotoxicity (TIC) can lead to early treatment discontinuation. The aim of this study was to evaluate: N-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), myoglobin, and selected biochemical and clinical factors as predictors of TIC. One hundred and thirty patients with HER2-positive BC receiving adjuvant trastuzumab therapy (TT) were enrolled. Measurement of cardiac markers and biochemical tests as well as echocardiography were performed prior to TT initiation and every three months thereafter. Cardiotoxicity leading to treatment interruption occurred in 24 patients (18.5%). While cardiotoxicity caused early treatment discontinuation in 14 patients (10.8%), the TIC resolved in 10 (7.7%) and TT was resumed. The most common complication was a decrease in left ventricular ejection fraction of more than 10% from baseline or below 50% (7.7%). In patients with TIC, there was no increase in the levels of NT-proBNP, myoglobin, and CK-MB. BMI, hypertension, ischemic heart disease, diabetes, age, cancer stage, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were shown to not have an effect on TIC occurrence. NT-proBNP, myoglobin, and CK-MB are not predictors of TIC. There is an ongoing need to identify biomarkers for TIC.

Introduction: Recently, the prognosis of patients with HER2‑positive breast cancer (BC) has improved significantly owing to the use of combined treatment modalities. However, systemic treatment is as-sociated with increased risk of cardiotoxicity., Objectives: We aimed to assess subclinical cardiac alterations during the final stage of adjuvant com-bined therapy, that is, trastuzumab therapy (TT), as potential predictors of late cardiac complications in patients with HER2‑positive BC., Patients and Methods: We enrolled 251 patients with HER2‑positive BC treated with a radical local therapy, adjuvant chemotherapy (anthracyclines or anthracyclines + taxanes), and immunotherapy (trastuzumab). Patients underwent 6 echocardiographic examinations: at baseline, during TT, and after TT, with assessment of left ventricular ejection fraction (LVEF), degree of valvular regurgitation, and cardiac chamber diameters., Results: Valvular fibrosis (28.4% of patients) was associated with older age, hypertension at baseline, and a higher degree of regurgitation during TT. Reduced LVEF, greater regurgitation, and larger cardiac chamber diameters were noted during TT. The patients who received higher anthracycline doses showed a greater degree of aortic insufficiency and a larger right ventricular diameter. Reduced LVEF during TT was associated with radiotherapy or chemotherapy and the degree of valvular regurgitation. Significantly larger diameters were observed in older patients and in those with comorbidities at baseline, high body mass index, and regurgitation., Conclusions: Asymptomatic subclinical cardiac alterations during TT may predict late cardiac complica-tions; however, longer follow‑up is necessary to confirm this hypothesis. Patients with HER2‑positive BC should be closely monitored for possible cardiac alterations during and after therapy to ensure optimal care and guide therapeutic decision‑making.

Kinase inhibitors (KIs) represent a growing class of drugs directed at various protein kinases and used in the treatment of both solid tumors and hematologic malignancies. It is a heterogeneous group of compounds that are widely applied not only in different types of tumors but also in tumors that are positive for a specific predictive factor. This review summarizes common cardiotoxic effects of KIs, including hypertension, arrhythmias with bradycardia and QTc prolongation, and cardiomyopathy that can lead to heart failure, as well as less common effects such as fluid retention, ischemic heart disease, and elevated risk of thromboembolic events. The guidelines for cardiac monitoring and management of the most common cardiotoxic effects of protein KIs are discussed. Potential signaling pathways affected by KIs and likely contributing to cardiac damage are also described. Finally, the need for further research into the molecular mechanisms underlying the cardiovascular toxicity of these drugs is indicated.

Transcutaneous electrical nerve stimulation (TENS) is the usage of a mild electrical current through electrodes that stimulate nerves. Patients with malignancies experience pain and chemotherapy-induced peripheral neuropathy. A systematic review was performed to find research evaluating the effect of TENS on these two common symptoms decreasing the quality of life in cancer patients. PubMed, the Cochrane Central Register of Controlled Trials and EMBASE were searched. Original studies, namely randomized controlled trials, quasi-randomized controlled trials and controlled clinical trials, published between April 2007 and May 2020, were considered. The quality of the selected studies was assessed. Seven papers were incorporated in a qualitative synthesis, with 260 patients in total. The studies varied in terms of design, populations, endpoints, quality, treatment duration, procedures and follow-up period. Based on the results, no strict recommendations concerning TENS usage in the cancer patient population could be issued. However, the existing evidence allows us to state that TENS is a safe procedure that may be self-administered by the patients with malignancy in an attempt to relieve different types of pain. There is a need for multi-center, randomized clinical trials with a good methodological design and adequate sample size.

Immune checkpoint inhibitors have significantly improved the prognosis of melanoma patients. However, these therapies may trigger unexpected immune-related adverse events (irAEs), which are challenging in making the proper diagnosis and providing treatment. Hematological toxicities are possible irAEs, but were poorly evaluated in clinical trials and treatment recommendations of this specific complications are limited. We present a stage IV melanoma patient who developed an extremely rare toxicity - hemophagocytic lymphohistiocytosis (HLH) after the 4th course of combined immunotherapy with nivolumab and ipilimumab. The patient was steroid resistant and only the treatment with various immunosuppressive agents provided control of the disease and finally melanoma regression. In this report, we evaluated the methods of HLH treatment and described our modification of available protocols. Immediate immunosuppression can be life-saving and due to rarity of this condition as well as lack of specific recommendations, every report is valuable for clinicians, especially when treatment was effective.

In 2018, a bi-partisan proposed draft legislation called the Verifying Accurate, Leading-edge IVCT Development (VALID) Act was released by Representative Larry Bucshon (Republican-Indiana) and Diana DeGette, (Democrat-Colorado). The VALID Act attempts to create a new framework for the oversight and regulations of both laboratory-developed testing procedures (commonly known as laboratory-developed tests) and In vitro diagnostic tests by the U.S. Food and Drug Administration. The potential impact of this new law if passed may be significant for clinical laboratories in terms of diagnostic test development and implementation. In this report, we review the background and key information that every clinical virologist should know about the VALID Act., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Systemic sclerosis (SSc) is a rare immune-mediated heterogenous entity characterised by excessive tissue fibrosis and vascular injury. Recently, increased risk of thromboembolic events has been documented in that disease. Our aim was to investigate prothrombotic plasma properties together with selected laboratory biomarkers of endothelial injury in SSc., Methods: In 56 clinically stable SSc patients and 67 well-matched controls we assessed plasma thrombin generation profile and measured circulating vascular cell adhesion molecule-1 (VCAM-1), cellular fibronectin (cFN), and thrombomodulin, as well as analysed their relationships with disease clinical parameters and autoimmune antibodies profile., Results: SSc was characterised by 18.3% increased endogenous thrombin potential (ETP), 14.5% higher thrombin peak (p<0.001 both, also after adjustment for potential confounders), and similar endothelial damage biomarkers, as compared to controls. Surprisingly, raised thrombin generation was related to the lower thrombomodulin and VCAM-1. Inflammatory markers, factor VIII activity, and blood eosinophilia predicted positively ETP, whereas platelet count and thrombomodulin had negative impact on that parameter in a multiple regression model. Intriguingly, patient group had also 6.7% extended lag-time (p=0.01 after adjustment for confounders) which was independently determined by higher thrombomodulin and cFN, as well as lower VCAM-1. Former cyclophosphamide therapy, thus more severe type of the disease was referred to the increased thrombin generation., Conclusions: SSc is characterised by enhanced thrombin generation potential which might contribute to the higher risk of thromboembolic events in that disease. Endothelium may play hereby an additional role, although large observational and experimental studies are needed to verify this hypothesis.

Aim: To evaluate treatment results in advanced/metastatic melanoma patients treated with anti-PD-1 immunotherapy in routine practice in oncology centers in Poland. Methods: Multicenter retrospective analysis included 499 patients with unresectable/metastatic (stage IIIC-IV) melanoma treated with anti-PD-1 in first-line therapy. Results: Estimated median overall survival (OS) and progression-free survival (PFS) were 19.9 and 7.9 months, respectively. Multivariate analysis confirmed that ECOG 0, no brain metastases, normal lactate dehydrogenase level and occurrence of immune-related adverse events (irAEs) were statistically significantly associated with improved OS and PFS. Any irAE occurred in 24% of patients. Grade 3 or Grade 4 irAEs occurred in 6% of patients. Conclusion: Analysis revealed a slightly worse OS in real-world treatment in comparison to clinical trials (KEYNOTE-006 and CheckMate 066). Polish population treatment results are similar to other studies of real-world data. PFS and ORR are similar in our research and clinical trials.

Background: Sensitive and high throughput molecular detection assays are essential during the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The vast majority of the SARS-CoV-2 molecular assays use nasopharyngeal swab (NPS) or oropharyngeal swab (OPS) specimens collected from suspected individuals. However, using NPS or OPS as specimens has apparent drawbacks, e.g. the collection procedures for NPS or OPS specimens can be uncomfortable to some people and may cause sneezing and coughing which in turn generate droplets and/or aerosol particles that are of risk to healthcare workers, requiring heavy use of personal protective equipment. There have been recent studies indicating that self-collected saliva specimens can be used for molecular detection of SARS-CoV-2 and provides more comfort and ease of use for the patients. Here we report the performance of QuantiVirus™ SARS-CoV-2 test using saliva as the testing specimens with or without pooling., Methods: Development and validation studies were conducted following FDA-EUA and molecular assay validation guidelines. Using SeraCare Accuplex SARS-CoV-2 reference panel, the limit of detection (LOD) and clinical performance studies were performed with the QuantiVirus™ SARS-CoV-2 test. For clinical evaluation, 85 known positive and 90 known negative clinical NPS samples were tested. Additionally, twenty paired NPS and saliva samples collected from recovering COVID-19 patients were tested and the results were further compared to that of the Abbott m2000 SARS-CoV-2 PCR assay. Results of community collected 389 saliva samples for COVID-19 screening by QuantiVirus™ SARS-CoV-2 test were also obtained and analyzed. Additionally, testing of pooled saliva samples was evaluated., Results: The LOD for the QuantiVirus™ SARS-CoV-2 test was confirmed to be 100-200 copies/mL. The clinical performance studies using contrived saliva samples indicated that the positive percentage agreement (PPA) of the QuantiVirus™ SARS-CoV-2 test is 100% at 1xLOD, 1.5xLOD and 2.5xLOD. No cross-reactivity was observed for the QuantiVirus™ SARS-CoV-2 test with common respiratory pathogens. Testing of clinical samples showed a positive percentage agreement (PPA) of 100% (95% CI: 94.6% to 100%) and a negative percentage agreement (NPA) of 98.9% (95% CI: 93.1% to 99.9%). QuantiVirus™ SARS CoV-2 test had 80% concordance rate and no significant difference (p = 0.13) between paired saliva and NPS specimens by Wilcoxon matched pairs signed rank test. Positive test rate was 1.79% for 389 saliva specimens collected from local communities for COVID-19 screening. Preliminary data showed that saliva sample pooling up to 6 samples (1:6 pooling) for SARS-CoV-2 detection is feasible (sensitivity 94.8% and specificity 100%)., Conclusion: The studies demonstrated that the QuantiVirus™ SARS-CoV-2 test has a LOD of 200 copies/mL in contrived saliva samples. The clinical performance of saliva-based testing is comparable to that of NPS-based testing. Pooling of saliva specimens for SARS-CoV-2 detection is feasible. Saliva based and high-throughput QuantiVirus™ SARS-CoV-2 test offers a highly desirable testing platform during the ongoing COVID-19 pandemic., Competing Interests: This commercial affiliation (to Diacarta Inc) does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Atrial fibrillation (AF) is a frequent comorbidity in malignant patients. Anticancer therapies complicate anticoagulant strategy. We evaluated the safety and efficacy of long-term use of direct oral anticoagulants (DOACs) in breast cancer women., Methods: In a prospective cohort study we enrolled 48 consecutive radically treated breast cancer women with AF (median age 63 [interquartile range 56-69] years, CHA 2 DS 2 -VASc 2 [2,3]) score) and adjuvant hormonal therapy. Thromboembolic complications (stroke, transient ischemic attack [TIA], venous thromboembolism [VTE]) and bleeding events (major and clinically relevant non-major bleeding [CRNMB]) were recorded in follow-up., Results: During a median follow-up of 40 (interquartile range 28-50.5) months 13 (27%) patients received apixaban, 22 (46%) rivaroxaban, and 13 (27%) dabigatran. One stroke (2.3%/year) and two CRNMBs (4.6%/year) were observed on apixaban. One TIA (1.3%/year), three major bleedings and two CRNMBs (6.7%/year, combined) were reported on rivaroxaban. Three VTE were documented in dabigatran treated individuals (7.8%/year), without any bleeding or cerebrovascular events. Women with thromboembolic events had higher body mass index (32 [29-33]) vs. 26 [24-29]) kg/m 2 , p = 0.02) and CHA 2 DS 2 -VASc score (3 [3]) vs. 2 [1-3]), p = 0.02). Most thromboembolic complications (n = 4, 80%) and all three major bleedings were observed in tamoxifen users, while three of four CRNMBs occurred on aromatase inhibitors. Mortality rates were low (apixaban, n = 1 [2.3%/year], rivaroxaban, n = 3 [5.22%/ year], and dabigatran, n = 2 [4%/ year]). No death was related to bleeding., Conclusions: This study suggests that DOACs are an effective and safe therapeutic option in breast cancer patients with AF during adjuvant hormonal therapy., Competing Interests: Declaration of Competing Interest We declare no conflict of interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Patients with systemic sclerosis experience endothelial dysfunction and damage even in the absence of clinical manifestations., Aim: To evaluate various methods for assessing the endothelial function for their applicability to clinical practice., Material and Methods: Forty-two patients (7 men and 35 women) with systemic sclerosis and 36 controls (11 men and 25 women) matched for age, sex, body mass index, smoking habit, and comorbidities were enrolled in the study. We assessed each participant for typical risk factors for cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1) and thrombomodulin together with flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography., Results: Patients with systemic sclerosis did not differ from controls in serum levels of VCAM-1 and thrombomodulin, however, the statistical analysis with adjustment for potential confounders revealed increased levels of thrombomodulin in the patients ( p = 0.03). They also had a 45% lower relative increase of FMD (FMD%), and 13% higher IMT ( p < 0.01, both, also after adjustment for potential confounders). In a simple regression model, lower FMD% was determined by age (β = -0.57, 95% confidence interval (CI): -0.72 to -0.43) and C-reactive protein levels (β = -0.38, 95% CI: -0.55 to -0.22). Thicker IMT was related to age (β = 0.64, 95% CI: 0.52-0.67), glomerular filtration rate (β = -0.34, 95% CI: -0.5 to -0.18), and blood thrombomodulin levels (β = 0.45, 95% CI: 0.13-0.76)., Conclusions: Patients with systemic sclerosis present with endothelial dysfunction which may be detected using ultrasonographic methods. The exact mechanism of observed abnormalities is unknown, but it is possibly related to the chronic inflammation and ischemia-reperfusion injury., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia Sp. z o. o.)

Respiratory tract infections are a common cause of visits to emergency departments and outpatient settings. Infections with influenza viruses A and B in particular, are responsible for significant morbidity and mortality in both pediatric and adult populations worldwide. A significant number of influenza diagnoses occur in the emergency departments with many being performed using rapid influenza diagnostic tests (RIDT) which have sensitivities as low as 30% depending on the specific RIDT and patient population. More recently, rapid molecular tests for the detection of influenza viruses A and B have become commercially available as point-of-care platforms. In the United States, several of these new tests are approved by the Food and Drug Administration as CLIA-waived tests. In this report, we review the data on the analytical and clinical performance of RIDTs and CLIA-waived molecular tests, present and discuss potential key challenges and opportunities for implementation of CLIA-waived molecular tests at or near point of care in the emergency departments and outpatient settings., (Copyright © 2019. Published by Elsevier B.V.)

The presence of detectable HIV-1 prior to the appearance of HIV-1-specific antibody was assessed in 41 incident infections that occurred during a 6-year prospective cohort study. All available antibody-negative samples (n = 138) and the first antibody positive sample (n = 41) were tested, under code, by the polymerase chain reaction (PCR) in two laboratories and by HIV-1 isolation in a third laboratory. Samples were available as long as 66 months and at least 18 months before seroconversion for 24/41 subjects. An equal number of time-matched control specimens from persistently seronegative homosexual men and 103 samples from normal blood donors were also tested under code. Samples with discordant results were subjected to coded repeat analysis along with appropriate controls. All but one of the 41 first antibody-positive specimens (97.6%) were PCR positive and 65% were isolation positive. Two control specimens from seronegative homosexual men were PCR positive and one was culture positive, but HLA typing provided clear evidence of specimen mix-up in the specimen archive. For 37/41 seroconvertors, all available antibody negative specimens were negative by both PCR and virus isolation. In three cases, the specimen obtained 6 months before seroconversion was PCR and isolation positive. One specimen, obtained 12 months before SC, was PCR positive and isolation negative but was determined to be the result of sample contamination. Both PCR and isolation were negative in this subject 6 months before SC. In conclusion, we were unable to detect immunosilent infection > 6 months before seroconversion in high-risk homosexual men.

Concordance between two primer pairs and the clinical sensitivity of a single primer pair-probe system were evaluated for a human immunodeficiency virus type 1 (HIV-1) polymerase chain reaction (PCR) assay. Six-hundred sixty-three clinically defined HIV-1 specimens were analyzed in a blind fashion for HIV-1 DNA using an optimized, well-characterized PCR assay. All samples were amplified in duplicate with each of two primer pairs targeting distinct, highly conserved regions within the HIV-1 gag genome. Amplified product was detected by oligomer hybridization using 32P-labeled probes. Correlation between PCR, culture, and serology data was achieved in 661 of 663 (99.7%) specimens. After initial analysis, discordant PCR results due to discrepancies between primer pairs were observed in 9 of 663 (1.4%) specimens. All nine specimens were resolved as negative on reevaluation. After retesting of discordant PCR results, concordance between the two primer pairs was achieved in 100% of samples. These data indicate that the two primer pair systems performed comparably and that good clinical sensitivity (100%) would be achieved using a single primer-probe system. Factors and procedures that influence the reproducibility and accuracy of this HIV-1 PCR assay are discussed.

The sensitivity and specificity of the polymerase chain reaction (PCR) for the detection of HIV-1 proviral DNA was determined in five laboratories with extensive experience in PCR testing. Five panels consisting of 105 HIV-1-seronegative specimens from regularly repeating blood donors with no risk factors for HIV infection and 99 HIV-1-seropositive and culture-positive specimens from a cohort of homosexual/bisexual men were sent under code to each laboratory. Amplification procedures and testing algorithms by which specimens were judged positive, negative, or indeterminate varied between laboratories. The average sensitivity for the five laboratories was 99.0%, with two laboratories achieving 100%. The average specificity was 94.7%, varying between 90.5 and 100%. The overall false-positive rate was 1.8%, the false-negative rate was 0.8%, and the indeterminate rate was 1.9%. Of 1,005 determinations made by the five laboratories, 32 (3.2%) were misclassifications. Most of the classification errors occurred in specimens from uninfected individuals and were distributed among the laboratories in such a way as to indicate laboratory error rather than the inherent reactivity of some samples. This emphasizes the need for standardization of PCR testing and caution in interpreting positive PCR reactions in HIV-1-seronegative persons.

Allele and genotype frequencies at the HLA-DQ alpha locus have been determined by the use of polymerase chain reaction (PCR) amplification and nonradioactive oligonucleotide probes. The probes define six alleles and 21 genotypes in a dot-blot format. A total of over 1,400 individuals from 11 populations has been typed by two different laboratories using this method. In contrast to some variable-number-of-tandem-repeat markers that have been used for identity determination, DQ alpha genotype frequencies do not deviate significantly from Hardy-Weinberg equilibrium in all populations studied. The distribution of alleles varies significantly between most of these populations. In Caucasians, the allele frequencies range from 4.3% to 28.5%. In this population, the power of discrimination is .94, and, for paternity determination, the power of exclusion is .642. These population data will allow the use of the HLA-DQ alpha marker in paternity determination, the analysis of individual identity in forensic samples, and anthropological studies.

Prostatic glycoprotein was detected in the vaginal fluid of a male pseudohermaphrodite with use of an enzyme-linked immunosorbent assay. Following orchiectomy, prostatic glycoprotein concentrations fell from levels greater than 60 to less than 10.0 ng/ml. The decline in prostatic glycoprotein levels postoperatively implies that prostatic glycoprotein expression is controlled by androgens.

Using a modified Salmonella typhimurium TA98 Ames-test system, more than 150 red, white and rose wines were analyzed for direct-acting and microsomal enzyme-enhanced mutagenic activity. The following conclusions were reached from analysis of this wine mutagenicity data base. White and rose wines, as well as grape juices, exhibited little or no detectable direct-acting or microsomal enzyme-enhanced mutagenic activity. However, red wine samples contained highly variable amounts of mutagens, ranging from undetectable to levels 30-fold above the sensitivity limit of the assay system. The variations in red wine mutagenicity were unrelated to grape variety, vintage, aging methods or production region. Hence, individual winery production practices must represent the most significant contribution to the variations observed.