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There is a growing prevalence of pancreatic cancer, accompanied by accelerated disease progression and diminished survival rates. Radical resection with clear margins remains the sole viable option for achieving a long-term cure in patients. In cases of advanced, unresectable, and metastatic disease, chemotherapy based on leucovorin, 5-fluorouracil, irinotecan, oxaliplatin, gemcitabine, or nab-paclitaxel represents the cornerstone of the treatment. Considering the limited treatment options available following initial therapy, the strategy of repurposing commonly prescribed drugs such as antihypertensives into anti-cancer therapies in palliative treatment represents a promising avenue for enhancing survival in patients with pancreatic ductal adenocarcinoma. The repurposing of existing drugs is typically a more cost-effective and expedient strategy than the development of new ones. The potential for antihypertensive drugs to be employed as adjunctive therapies could facilitate a more comprehensive treatment approach by targeting multiple pathways involved in cancer progression and acquired resistance to treatment. Antihypertensive medications, particularly those belonging to the pharmacological classes of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and calcium channel blockers, are commonly prescribed and have well-established safety profiles, particularly among patients with pancreatic cancer who are affected by multiple comorbidities. Therefore, we emphasize the preclinical and clinical evidence supporting the use of antihypertensive agents in the treatment of pancreatic cancer, emphasizing their beneficial chemosensitizing effects.

Introduction: The aim of the study was to assess prognostic factors associated with an increased risk of recurrence of hepatocellular carcinoma (HCC) after radical treatment., Materials and Methods: This is a retrospective, single-center analysis of data on HCC recurrence in patients who underwent radical treatment. Molecular tumor characteristics, baseline laboratory results and hepatic viral status were analyzed., Results: Data from 111 patients were included in the analysis. The most important prognostic factors for recurrence were vascular microinvasion (HR 4.54; 95 % CI 1.769-11.681; p 0.001), baseline white blood count (HR 2.13; 95 % CI 1.261-3.567; p 0.004) and baseline alpha-fetoprotein (HR 1.00009; 95 % CI 1.000001-1.00002; p 0.034). Microvascular invasion was only prognostic factor which correlate significantly with the overall survival (HR 5.04, 95 % CI 2.352-12.413; p < 0.001). PD-L1 expression was confirmed in 4 patients and all of them developed a disease recurrence. However, there was no statistically significant assosciation with prognosis. The presence of CD68 tumor-associated macrophages was confirmed in 62 patients, ranging from 5 % to 40 %. Analysis showed that CD68 was not associated with the risk of recurrence of HCC., Conclusions: The results confirm that microvascular invasion is the most important factor associated with an increased risk of hepatocellular carcinoma recurrence and death, while PD-L1 and CD68 expression did not have an impact on patient prognosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background: The aim of this study was to determine the differences in diffusion-weighted imaging (DWI) and dynamic contrast enhancement (DCE) parameters between patients with peritoneal high-grade serous ovarian cancer (HGSOC) recurrence with BRCA mutations (BRCAmut) or BRCA wild type (BRCAwt)., Materials and Methods: We retrospectively analyzed the abdominal and pelvic magnetic resonance (MR) images of 43 patients suspected of having recurrent HGSOC, of whom 18 had BRCA1/2 gene mutations. Patients underwent MRI examination via a 1.5 T MRI scanner, and the analyzed parameters were as follows: apparent diffusion coefficient (ADC), time to peak (TTP) and perfusion maximum enhancement (Perf. Max. En.)., Results: The mean ADC in patients with BRCAwt was lower than that in patients with BRCAmut: 788.7 ( SD : 139.5) vs. 977.3 ( SD : 103), p -value = 0.00002. The average TTP value for patients with BRCAwt was greater than that for patients with mutations: 256.3 ( SD : 50) vs. 160.6 ( SD : 35.5), p -value < 0.01. The Perf. Max. En. value was lower in the BRCAwt group: 148.6 ( SD : 12.3) vs. 233.6 ( SD : 29.2), p -value < 0.01., Conclusion: Our study revealed a statistically significant correlation between DWI and DCE parameters in examinations of peritoneal metastasis in patients with BRCA1/2 mutations. Adding DCE perfusion to the MRI protocol for ovarian cancer recurrence in patients with BRCAmut may be a valuable tool.

Introduction: Analysis of selected MRI parameters in initial MRI for the characterization of ovarian masses enables differentiation between mucinous ovarian carcinoma and metastatic ovarian tumors. Material and Methods: A prospective analysis of contrast-enhanced MRI of patients with suspected ovarian masses diagnosed in ultrasound and CT examination. Morphological criteria, such as the size of lesion, bilateral location, presence of "mille-feuille sign", so-called Seidman criteria, as well as the diffusion weighted imaging and dynamic contrast enhancement of each lesion, were evaluated. Patients were allocated into two groups; the first group contained patients with mucinous ovarian cancer, and the second group contained patients with metastatic ovarian tumors. Results: A total of 35 patients were enrolled into the study. Median age was 49 in the first group and 59 in the second group of patients ( p = 0.04). In the first group, all patients (100%) had unilateral lesions, and in the second group, 94% had bilateral tumors ( p < 0.000001). In the first group, a tumor size equal or greater than 10 cm was present in 80% of patients, and the same was true for 21% of patients in the second group. The mille-feuille sign was present in 30% of patients from the first group and in 64% of patients from the second group. In the first group of patients, TTP was 410 and Perf.Max Enhancement was 141; in the second group, they were, respectively, 154 and 167 ( p = 0.0001 and p = 0.5). Median ADC values in the first group were significantly higher in the first group than in the second group ( p < 0.01). Conclusions: Significant differences in TTP and ADC values as well as in Seidman criteria enable reliable differentiation between the analyzed groups of tumors.

Purpose: Pancreatic cancer remains a significant public health challenge, with poor long-term outcomes due to the lack of effective treatment options. Repurposing commonly used clinical drugs, such as ACE inhibitors, ARBs, CCBs, and metformin, may enhance the efficacy of chemotherapy and offer a promising therapeutic strategy for improving patient outcomes., Methods: A retrospective analysis of concomitant treatment with ACE-Is, ARBs, CCBs, and metformin alongside gemcitabine chemotherapy in patients with pancreatic cancer was conducted. Treatment responses were evaluated, with overall survival (OS) estimated using the Kaplan-Meier method. Additionally, the Cox proportional hazards model was employed to assess the impact of these specific agents on patient survival., Results: 4628 patients with various stages of pancreatic cancer were identified in the database between 2007 and 2016. The estimated overall survival (OS) in the analyzed group was 6.9 months (95% CI 6.4-7). The use of any of the analyzed drugs was associated with a significant improvement in mOS of 7.5 months (95% CI 6.8-7.8) vs. 6.7 months (95% CI 6.4-7.0) for patients who did not have additional treatment (p < 0.0001). ARBs, ACE-Is, CCBs, and metformin varied in their effectiveness in prolonging mOS among patients. The longest mOS of 8.9 months (95% CI 7.7-11.6) was observed in patients receiving additional therapy with ARBs, while the shortest mOS of 7.7 months (95% CI 6.5-8.9) was achieved by patients receiving metformin. In the adjusted Cox analysis, metformin was associated with a significantly weaker effect on mOS (p = 0.029). A particularly interesting trend in prolonging 5-year survival was demonstrated by ARBs and CCBs with 14.1% (95% CI 9-22%) and 14.8% (95% CI 11.1-19.6%), respectively, compared to patients not taking these drugs, who achieved a 5-year OS of 3.8% (95% CI 3.2-4.4%)., Conclusion: Our results demonstrate a significant positive impact of ARBs, ACE inhibitors, and CCBs on survival in patients with pancreatic cancer treated with gemcitabine. The addition of these inexpensive and relatively safe drugs in patients with additional comorbidities may represent a potential therapeutic option in this indication. However, prospective clinical trials to evaluate the optimal patient population and further studies to determine the potential impact of these agents on chemotherapy are necessary., (© 2024. The Author(s).)

Hepatocellular carcinoma is one of the most common cancers worldwide. Despite progress in treatment, recurrence after radical treatment is common, and the prognosis remains poor for patients with advanced disease. Therefore, there is a need to identify prognostic and predictive factors for the response to therapy or more intensive surveillance or treatment. Because the tumor microenvironment plays a crucial role in the development of cancer and metastasis, it is a crucial need to understand processes that are involved in carcinogenesis. Within the microenvironment, several immune cells with different roles are present. One of the most important of these is tumor-associated macrophages. These cells may exert either antitumor or protumor roles. Several studies have suggested that tumor-associated macrophages can be used as prognostic markers. Furthermore, they may be involved in resistance to immunotherapy or systemic treatment. As they play an important role in cancer development, tumor-associated macrophages are also a good target for therapy. In this review, we briefly summarize recent progress on knowledge regarding the basic molecular characteristics, impact on prognosis and potential clinical implications of tumor-associated macrophages in hepatocellular carcinoma., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Platelets (PLT) have a role in the pathogenesis, progression, and prognosis of hepatocellular carcinoma (HCC) and could represent a readily measurable laboratory parameter to enhance the comprehensive evaluation of HCC patients., Methods: The PubMed, Web of Science, and Scopus databases were searched with a focus on survival as well as patient and tumor-specific characteristics in correlation to reported PLT counts. Survival outcomes were analyzed with both common-effect and random-effects models. The hazard ratio (HR) and its 95% confidence interval (CI) from analyzed trials were incorporated. Studies that did not provide survival data but focused on platelet count correlation with HCC characteristics were reviewed., Results: In total, 26 studies, including a total of 9403 patients, met our criteria. The results showed that thrombocytopenia in HCC patients was associated with poor overall survival (common-effect HR = 1.15, 95% CI: 1.06-1.25; random-effect HR = 1.30, 95% CI: 1.05-1.63). Moreover, three studies reveal significant correlations between PLT indices and tumor characteristics such as size, foci number, and etiology of HCC development., Conclusion: Our meta-analysis confirmed that PLT count could act as a prognostic marker in HCC, especially with a PLT count cut off <100 × 10 3 /mm 3 . Further prospective studies focusing on the role of PLT in clearly defined subgroups are necessary.

Background Chronic kidney disease (CKD) coexisting with atrial fibrillation (AF) increases the risk of hemorrhage and ischemia. The study aimed to determine the relationship between different CKD stages and clinical outcomes of patients suffering from both CKD and AF and to determine the predictors of outcome. Methods The data was derived from multicenter CRAFT trial (NCT02987062). We have conducted a retrospective analysis of hospital records of 2663 AF patients divided in three groups according to their estimated glomerular filtration rate (eGFR) which was <30ml/min/1,73 m2 for group I (n=63), ≥30 and <60 ml/min/1,73 m 2 for group II (n=947) and ≥60 ml/min/1,73 m 2 for group III (n=1653). The primary study endpoint was major adverse event (MAE) during the mean four-year follow-up. Results The highest rate of MAE was observed in group I followed by group II and III. The rate of all-cause death was 60% in group I, 32% in group II and 15% in group III (p<0.001). Bleeding complications occurred in 25% of patients from group I, 23% from group II and 21% from group III (p=0.14). Thromboembolic events occurred in those groups at the rate of 21%, 14% and 12% respectively (p=0.011). The risk of death was 5 times higher in patients with eGFR<30 treated with vitamin K antagonists (VKA) (HR: 5.016, 95% CI: 1.533-16.417; p=0.007). Conclusions AF patients with CKD are at higher risk of MAE and that risk depends on the CKD stage. VKA treatment was linked to a higher mortality in AF patients with the lowest eGFR values., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Anemia and iron deficiency (ID) are common complications in patients with pancreatic ductal adenocarcinoma (PDAC), but their underlying causes remain unclear. This study investigated the incidence and characteristics of anemia and micronutrient deficiencies in PDAC patients before initiating chemotherapy. A total of 103 PDAC patients were included, comprising 67 in the palliative and 36 in the adjuvant groups. The overall incidence of anemia was 42.7% ( n = 44), with comparable rates in both groups. Normocytic and normochromic anemia were predominant, with mild and moderate cases observed in 32% and 10.7% of the cohort, respectively. ID was evident in 51.4% of patients, with absolute ID more frequent in the adjuvant than in the palliative group (19.4% vs. 13.4%). Functional ID occurred more often in the palliative than in the adjuvant group (41.8% vs. 25%). Vitamin B12 and folate deficiency occurred in <5% ( n = 5) of patients. Furthermore, 8.7% ( n = 9) of patients had chronic kidney disease and anemia. To elucidate mechanisms of iron deficiency, the study explored the expression of iron regulators (hepcidin (HEP), ferroportin (FPN), and ZIP14 protein) and mitochondrial mass in PDAC tissue with immunohistochemical (IHC) staining and Perl's Prussian blue to detect iron deposits on available tumor samples ( n = 56). ZIP14 expression was significantly higher in less advanced tumors ( p = 0.01) and correlated with mitochondrial mass ( p < 0.001), potentially indicating its role in local iron homeostasis. However, no significant impact of tissue iron regulators on patient survival was observed. Perl's Prussian blue staining revealed iron deposits within macrophages, but not in pancreatic duct cells. Furthermore, the GEPIA database was used to compare mRNA expression of iron regulators (HEP, FPN, and ZIP14) and other genes encoding iron transport and storage, including Transferrin Receptor Protein 1 (TfR1) and both ferritin chain subunits (FTH and FTL), in PDAC and normal pancreatic samples. FPN, TfR1, FTH, and FTL showed higher expression in tumor tissues, indicating increased iron usage by cancer. ZIP14 expression was higher in the pancreas than in PDAC and was correlated with FPN expression. The study highlights the importance of baseline iron status assessment in managing PDAC patients due to the high incidence of anemia and iron deficiency. Furthermore, ZIP14, in addition to HEP and FPN, may play a crucial role in local iron homeostasis in PDAC patients, providing valuable insights into the underlying mechanisms of iron dysregulation.

Radical resection is the only curative treatment for pancreatic cancer. However, only up to 20% of patients are considered eligible for surgical resection at the time of diagnosis. Although upfront surgery followed by adjuvant chemotherapy has become the gold standard of treatment for resectable pancreatic cancer there are numerous ongoing trials aiming to compare the clinical outcomes of various surgical strategies (e.g., upfront surgery or neoadjuvant treatment with subsequent resection). Neoadjuvant treatment followed by surgery is considered the best approach in borderline resectable pancreatic tumors. Individuals with locally advanced disease are now candidates for palliative chemo- or chemoradiotherapy; however, some patients may become eligible for resection during the course of such treatment. When metastases are found, the cancer is qualified as unresectable. It is possible to perform radical pancreatic resection with metastasectomy in selected cases of oligometastatic disease. The role of multi-visceral resection, which involves reconstruction of major mesenteric veins, is well known. Nonetheless, there are some controversies in terms of arterial resection and reconstruction. Researchers are also trying to introduce personalized treatments. The careful, preliminary selection of patients eligible for surgery and other therapies should be based on tumor biology, among other factors. Such selection may play a key role in improving survival rates in patients with pancreatic cancer., Competing Interests: The authors declare no conflicts of interest.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer diagnosed worldwide. After a decade of stagnation, several novel compounds have recently been shown to be effective in the treatment of HCC. Since immunotherapy is associated with important clinical benefits in some, but not all patients, it is essential to identify reliable predictive biomarkers. As the complex interplay between hepatocytes and immune cells is highly dependent on the tumor microenvironment, the tumor microenviroment has been suggested to be an important factor associated with the response to therapy and is currently being extensively investigated. Within this network, several important factors should be highlighted. Most of the cells are hepatocytes, but fibroblasts, endothelial cells, and immune cells are also present. Tumor-infiltrating leukocytes include several populations of cells and each of them plays a role in forming the tumor environment. Some of these cells may have antitumor effects, whereas others may be associated with the progression of the disease. The most important subsets include tumor-associated macrophages, tumor-associated neutrophils, and lymphocytes. These groups are described in the present review. The immune response is controlled by immune checkpoint molecules. One of the most important molecules involved in this checkpoint process seems to be the programmed death-1 (PD-1) receptor, which typically is induced on activated T cells, natural killer (NK) cells, B cells, and antigen-presenting cells. On the other hand, programmed death ligand 1 (PD-L1) is expressed by tumor cells, hepatocytes and hepatic stellate cells, and Kupffer cells or liver sinusoidal cells. Complex interactions between ligands and receptors are dependent on the signals from the microenvironment leading to either cancer development or apoptosis. Evidence from several studies indicates that patients with higher expression levels of PD-L1 on tumor cells or immune cells are more likely to achieve beneficial results from treatment with checkpoint blockers. This review focuses on the basic information regarding the microenvironment and its components, particularly on immune system involvement., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Gryziak et al.)

(1) Background: Administrative data allows for time- and cost-efficient acquisition of large volumes of individual patient data invaluable for evaluation of the prevalence of diseases and clinical outcomes. The aim of the study was to evaluate the accuracy of data collected from the Polish National Health Fund (NHF), from a researcher's perspective, in regard to a cohort of atrial fibrillation patients. (2) Methods: NHF data regarding atrial fibrillation and common cardiovascular comorbidities was compared with the data collected manually from the individual patients' health records (IHR) collected in the retrospective CRAFT registry (NCT02987062). (3) Results: Data from the NHF underestimated the proportion of patients with AF (NHF = 83% vs. IHR = 100%) while overestimating the proportion of patients with other cardiovascular comorbidities in the cohort. Significantly higher CHA2DS2VASc (Median, [Q1-Q3]) (NHF: 1, [0-2]; vs. IHR: 1, [0-1]; p < 0.001) and HAS-BLED (Median, [Q1-Q3]) (NHF: 4, [2-6] vs. IHR: 3, [2-5]; p < 0.001) scores were calculated according to NHF in comparison to IHR data, respectively. (4) Conclusions: Clinical researchers should be aware that significant differences between IHR and billing data in cardiovascular research can be observed which should be acknowledged while drawing conclusions from administrative data-based cohorts. Natural Language Processing of IHR could further increase administrative data quality in the future.

Heart failure (HF) is a common disease that causes significant limitations on the organism's capacity and, in extreme cases, leads to death. Clinically, iron deficiency (ID) plays an essential role in heart failure by deteriorating the patient's condition and is a prognostic marker indicating poor clinical outcomes. Therefore, in HF patients, supplementation of iron is recommended. However, iron treatment may cause adverse effects by increasing iron-related apoptosis and the production of oxygen radicals, which may cause additional heart damage. Furthermore, many knowledge gaps exist regarding the complex interplay between iron deficiency and heart failure. Here, we describe the current, comprehensive knowledge about the role of the proteins involved in iron metabolism. We will focus on the molecular and clinical aspects of iron deficiency in HF. We believe that summarizing the new advances in the translational and clinical research regarding iron deficiency in heart failure should broaden clinicians' awareness of this comorbidity.

The tumor microenvironment is the space between healthy tissues and cancer cells, created by the extracellular matrix, blood vessels, infiltrating cells such as immune cells, and cancer-associated fibroblasts. These components constantly interact and influence each other, enabling cancer cells to survive and develop in the host organism. Accumulated intermediate metabolites favoring dysregulation and compensatory responses in the cell, called oncometabolites, provide a method of communication between cells and might also play a role in cancer growth. Here, we describe the changes in metabolic pathways that lead to accumulation of intermediate metabolites: lactate, glutamate, fumarate, and succinate in the tumor and their impact on the tumor microenvironment. These oncometabolites are not only waste products, but also link all types of cells involved in tumor survival and progression. Oncometabolites play a particularly important role in neoangiogenesis and in the infiltration of immune cells in cancer. Oncometabolites are also associated with a disrupted DNA damage response and make the tumor microenvironment more favorable for cell migration. The knowledge summarized in this article will allow for a better understanding of associations between therapeutic targets and oncometabolites, as well as the direct effects of these particles on the formation of the tumor microenvironment. In the future, targeting oncometabolites could improve treatment standards or represent a novel method for fighting cancer.

In heart failure, iron deficiency is a common comorbid disease that negatively influences exercise tolerance, number of hospitalizations and mortality rate, and this is why iron iv supplementation is recommended. Little is known about the changes in iron-related proteins in the human HF myocardium. The purpose of this study was to assess iron-related proteins in non-failing (NFH) vs. failing (FH) human myocardium. The study group consisted of 58 explanted FHs; control consisted of 31 NFHs unsuitable for transplantation. Myocardial proteins expressions: divalent metal transporter (DMT-1); L-type calcium channel (L-CH); transferrin receptors (TfR-1/TfR-2); ferritins: heavy (FT-H) or light (FT-L) chain, mitochondrial (FT-MT); ferroportin (FPN), regulatory factors and oxidative stress marker: 4-hydroxynonenal (4-HNE). In FH, the expression in almost all proteins responsible for iron transport: DMT-1, TfR-1, L-CH, except TfR-2, and storage: FT-H/-L/-MT were reduced, with no changes in FPN. Moreover, 4-HNE expression (pg/mg; NFH 10.6 ± 8.4 vs. FH 55.7 ± 33.7; p < 0.0001) in FH was increased. HNE-4 significantly correlated with DMT-1 (r = -0.377, p = 0.036), L-CH (r = -0.571, p = 0.001), FT-H (r = -0.379, p = 0.036), also FPN (r = 0.422, p = 0.018). Reducing iron-gathering proteins and elevated oxidative stress in failing hearts is very unfavorable for myocardiocytes. It should be taken into consideration before treatment with drugs or supplements that elevate free oxygen radicals in the heart.

Introduction: Atrial fibrillation (AF) is associated with increased hospitalization. Objectives: We aimed to compare long-term outcomes in patients with AF hospitalized in academic and district hospitals. Patients and methods: This retrospective observational study included data from the Multicenter Experience in Atrial Fibrillation Patients Treated with Oral Anticoagulants (CRAFT; NCT02987062) study which included AF patients hospitalized between 2011 and 2016 in academic and district hospitals. The primary end point was a major adverse event (MAE) defined as all-cause death and thromboembolic and hemorrhagic events during the median 4-year follow-up. Results: We analyzed 2983 patients with AF: 2271 (76%) from academic and 712 (24%) from district hospitals. Patients treated in district hospitals, as compared with patients treated in academic hospitals, more often experienced MAEs (53% vs 37%; P <⁠0.001), all-cause death (40% vs 24%; P <⁠0.001), and thromboembolic events (13% vs 7.8%; P <⁠0.001), with similar rates of hemorrhagic events (15% vs 15%; P = 1.00). In multivariable logistic regression, female sex, coronary artery disease, smoking, and antiplatelet drug therapy were associated with greater likelihood of thromboembolic events in academic hospitals. Heart failure, renal failure, and vitamin K antagonist (in academic hospitals), and coronary artery disease (in district hospitals) were associated with greater likelihood of hemorrhagic events. District (vs academic) conditions were associated with higher risk of MAEs and all-cause death in men and those with low risk of bleeding, and with higher incidence of thromboembolic events in women, elderly patients, and those with high risk of bleeding and with diabetes. Conclusions: Patients with AF treated at district hospitals had worse long-term outcomes than those treated in academic conditions.

Background: Absolute neutrophil count (ANC) below 1.5 G/l or 1 G/l is commonly used as a factor to determine the decision to administer antineoplastic treatment including chemotherapy and novel agents to cancer patients. This practice is based on observations that below this ANC, there is an increased risk of bacterial and fungal infection. This is further based on the assumption that this parameter always correctly reflects the true shortage of these germ-fighting cells in patients. In reality, the circulating pool of neutrophils is only one of four reservoirs (bone marrow, circulating, marginal and tissue pools) and its size is influenced not only by shortage but also by transient shift of cells between these reservoirs. The aim of this study was to evaluate whether repeated blood collection affects ANC in the patient., Methods: We retrospectively analysed the medical records of cancer patients with 0.8 G/l ≤ ANC < 1.5 G/l in whom CBC was repeated based on the physician's decision, which was done on the same day roughly 2 h after the first one., Results: The patients at the time of repeating CBC had consumed breakfast. In 31 out of 32 patients, ANC exceeded 1 G/l or 1.5 G/l and antineoplastic treatment was administered as originally planned. There were no infectious complications observed., Conclusion: Cancer patients should not be fasting prior to blood collection, with the exception of special and rare situations. To achieve the maximum clinical benefit, delays and/or reductions of antineoplastic treatment should be avoided wherever possible. Pseudoneutropenia is an unnecessary reason for postponing chemotherapy.

Background: We aimed to compare long-term outcomes in Polish patients with atrial fibrillation (AF) according to oral anticoagulation (OAC) type and to evaluate the predictive value of common thromboembolic and bleeding risk scores., Methods: Data from the CRAFT trial (NCT02987062) were included. The primary study endpoint was major adverse event (MAE; all-cause death, thromboembolic and hemorrhagic event) during the mean four-year follow-up period., Results: Out of 2983 patients with available follow-up data, 1686 (56%) were prescribed with vitamin K antagonist (VKA), 891 (30%) with rivaroxaban and 406 (14%) with dabigatran. Predominance of elderly and female patients with previous history of thromboembolic and hemorrhagic events was observed within rivaroxaban (vs. other OAC) group. Higher rate of MAEs and its components was observed in patients on VKA followed by rivaroxaban as compared to patients on dabigatran (43% vs. 42% vs. 31%, p < 0.01). After group matching based on clinical characteristics, higher risk of hemorrhagic events in VKA (vs. dabigatran) and rivaroxaban (vs. dabigatran) group were observed. The available thromboembolic (CHA 2 DS 2 -VASs, ATRIA, R 2 CHADS 2 ) and bleeding (HAS-BLED, ATRIA, ORBIT) risk scores showed poor prediction value., Conclusions: Despite no difference in the thromboembolic event rate, treatment with VKA and rivaroxaban was associated with a significant increase in the risk of hemorrhagic events.

Purpose: Prostate-specific membrane antigen (PSMA) is not only highly expressed on the surface prostate cancer cells but is also elevated during angiogenesis in other cancer cell types, including hepatocellular carcinoma (HCC). This study aimed to evaluate the feasibility of using PET/CT imaging with [ 68 Ga]Ga-PSMA-11 in HCC and its impact on patient management., Methods: Fifteen patients (13 men and two women; aged 55.6 ± 18.2 years) with HCC were enrolled in this prospective, single-institution study. All patients underwent contrast-enhanced MRI/CT, [ 68 Ga]Ga-PSMA-11 PET/CT, and histopathological verification of lesions., Results: No radiopharmaceutical-related adverse events were noted. Visual interpretation showed increased accumulation of [ 68 Ga]Ga-PSMA-11 in all HCC patients. The tumor-to-liver ratio (TLR) was 3.6 ± 2.1, and the maximal standardized uptake value (SUV max ) was 13.5 ± 7.1. There were no significant differences in the SUVs or TLR between newly diagnosed and recurrent patients. No statistically significant relationship was found between serum concentration of tumor markers (i.e., AFP, CA 19-9, CEA) and PET parameters. Results of the [ 68 Ga]Ga-PSMA-11 PET/CT changed the treatment strategy in five (33%) patients. PSMA staining showed visible heterogeneity in terms of intensity and distribution: the reaction was weak and only observed in a few vessels in pseudoglandular patterns of HCC, while it was homogeneously strong, with some hot spots, in trabecular patterns of HCC., Conclusion: [ 68 Ga]Ga-PSMA-11 PET/CT can detect PSMA expression in vivo in patients with HCC and is useful for guiding treatment strategies. Further investigation of the clinical utility of this method in HCC is warranted.

According to data provided by WHO (World Health Organization), hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths worldwide. Since the approval of sorafenib in 2008, several trials have assessed other particles for the treatment of HCC, but few have proven to be effective. ESMO (European Society for Medical Oncology) guidelines have been changed several times recently. This systematic review aims to describe both successful and failed trials of systemic treatments for HCC. Methods: We examined randomized, phase III trials of first- and second-line treatments in adults, identifying 23 fully-published trials and 2 reported as abstracts. The latest advances in immunotherapy were also briefly discussed. Conclusions: The landscape of HCC treatment has changed significantly in recent years. Several small molecule inhibitors currently form the core of HCC treatment; however, immunotherapy is now emerging as a promising treatment option., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The retinoids are a group of compounds including vitamin A and its active metabolite all-trans-retinoic acid (ATRA). Retinoids regulate a variety of physiological functions in multiple organ systems, are essential for normal immune competence, and are involved in the regulation of cell growth and differentiation. Vitamin A derivatives have held promise in cancer treatment and ATRA is used in differentiation therapy of acute promyelocytic leukemia (APL). ATRA and other retinoids have also been successfully applied in a variety of dermatological conditions such as skin cancer, psoriasis, acne, and ichthyosis. Moreover, modulation of retinoic acid receptors and retinoid X (or rexinoid) receptors function may affect dermal cells. The studies using complex genetic models with various combinations of retinoic acid receptors (RARs) and retinoid X (or rexinoid) receptors (RXRs) indicate that retinoic acid and its derivatives have therapeutic potential for a variety of serious dermatological disorders including some malignant conditions. Here, we provide a synopsis of the main advances in understanding the role of ATRA and its receptors in dermatology.

Background: Heart failure patients presenting with iron deficiency can benefit from systemic iron supplementation; however, there is the potential for iron overload to occur, which can seriously damage the heart. Therefore, myocardial iron (M-Iron) content should be precisely balanced, especially in already failing hearts. Unfortunately, the assessment of M-Iron via repeated heart biopsies or magnetic resonance imaging is unrealistic, and alternative serum markers must be found. This study is aimed at assessing M-Iron in patients with advanced heart failure (HF) and its association with a range of serum markers of iron metabolism., Methods: Left ventricle (LV) myocardial biopsies and serum samples were collected from 33 consecutive HF patients (25 males) with LV dysfunction (LV ejection fraction 22 (11) %; NT-proBNP 5464 (3308) pg/ml) during heart transplantation. Myocardial ferritin (M-FR) and soluble transferrin receptor (M-sTfR1) were assessed by ELISA, and M-Iron was determined by Instrumental Neutron Activation Analysis in LV biopsies. Nonfailing hearts ( n = 11) were used as control/reference tissue. Concentrations of serum iron-related proteins (FR and sTfR1) were assessed., Results: LV M-Iron load was reduced in all HF patients and negatively associated with M-FR ( r = -0.37, p = 0.05). Of the serum markers, sTfR1/logFR correlated with ( r = -0.42; p = 0.04) and predicted (in a step-wise analysis, R 2 = 0.18; p = 0.04) LV M-Iron. LV M-Iron load ( μ g/g) can be calculated using the following formula: 210.24-22.869 × sTfR1/logFR., Conclusions: The sTfR1/logFR ratio can be used to predict LV M-Iron levels. Therefore, serum FR and sTfR1 levels could be used to indirectly assess LV M-Iron, thereby increasing the safety of iron repletion therapy in HF patients., Competing Interests: There are no potential conflicts of interest, including related consultancies, shareholdings, and funding grants., (Copyright © 2020 Przemysław Leszek et al.)

Introduction: Multiple myeloma is the third most common blood cancer in Europe and accounts for approx. 10-15% of these cancers. The objective of this study was to determine the incidence, prevalence, mortality and survival in multiple myeloma (ICD code: C90.0) patients in Poland in the years 2008-2017., Material and Methods: The analysis used the data on healthcare services provided to patients with multiple myeloma defined with the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) code C90.0 and reported by healthcare entities to the National Health Fund (NFZ)., Results: In 2009, the C90.0 incidence per 100,000 inhabitants was 6.4, while in 2017 it was 8.3. The prevalence in the same period increased by 76%, from 13.6/100,000 to 23.9/100,000. The mortality to prevalence ratio gradually decreased from 78% in 2008 to 22.8% in 2017. The 1-year, 3-year and 5-year survival rates in patients with this diagnosis made in the years 2009 and 2013 were 70.5%, 51.5% and 40.2% versus 78.4%, 60.3% and 48.3%, respectively., Conclusions: The incidence and prevalence of multiple myeloma and survival rates in Poland were continuously increasing in the studied period. These trends may result from the aging of Polish society, better recognisability of multiple myeloma and/or improved access to increasingly more effective therapies in Poland. The impact of these factors on the epidemiology of multiple myeloma requires further studies., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)

Hematopoietic stem cell transplantation (HSCT) is an aggressive method of treatment affecting patient's homeostasis. The aim of the study was to evaluate the initial nutritional status of HSCT patients and nutritional status in early posttransplantation period. The prospective study included 100 consecutive patients with hematological malignancies subjected to HSCT. The nutritional status evaluation was made using the nutritional screening scales, anthropometric and biochemical parameters, as well. On the day +7 following HSCT significant decrease in concentration of total protein (5.8 g/dl), albumin (3.6 g/dl) and transferrin (165 mg/dl) were observed (P < 0.001), although the mean body mass/BMI were within the normal range. On the day +14, the biochemical parameters of the nutritional status were even lower (P < 0.001). Poorer nutritional status was associated with worse performance status and mucositis escalation. The adequate nutritional support plan is important element of the whole transplantation procedure.

Background: Cancer disease is usually associated with impaired nutritional status, which is one of the factors contributing to deterioration of the results of surgery, chemotherapy or radiotherapy., Objectives: The aim of the study was to determine whether nutritional support with high protein (ONS) in adult oncologic patients in the first step of cancer cachexia-asymptomatic precachexia, has an influence on the toxicity of systemic therapy. However, secondary endpoints were established: to determine whether high protein ONS influences the nutritional status, the quality of life, and the performance status., Materials and Methods: A total of 114 persons aged 40-84 years old with colorectal cancer were examined. Based on the randomization, 47 patients were qualified to the interventional group (ONS group) and 48 to Control group. To evaluate the nutritional status NRS-2002 (Nutritional Risk Screening), SGA (Subjective Global Assessment), SCRINIO (SCReenIng the Nutritional status In Oncology) Working Group classification, VAS (Visual Analog Scale) for appetite was used. FAACT (Functional Assessment of Anorexia/Cachexia Therapy) questionnaire was used for assessment of the quality of life. The health status of patients was evaluated based on the Karnofsky Performance Scale. Anthropometric measurements were done., Results: Severe complications of chemotherapy, which caused the end of treatment, a slight complication of the gastrointestinal tract such as diarrhea grade 2 according to ECOG (Eastern Cooperative Oncology Group) score regardless of the studied group, were observed. There were no statistical differences in the number and severity of the observed complications, i.e., neutropenia, leucopenia, thrombocytopenia, anemia, abdominal pain, nausea and vomiting, and diarrhea. During the follow-up the significant changes of SGA, VAS, albumin and prealbumin were observed between groups. In the ONS group an improvement in nutritional status was noticed (increased appetite VAS, p = 0.05; increased points in SGA, p = 0.015, and increased levels of albumin and prealbumin, p = 0.05). In Control group nutritional status was stable during observation. The performance status and quality of life were stable in both groups. No statistical differences between groups (ONS vs. Control) in the numbers for disqualification, resignation, delay in treatment, or dose reduction were observed., Conclusions: Results of the study did not indicate that nutritional support in precachectic oncologic patients influenced the toxicity of systemic therapy. High protein nutritional support improved nutritional status assessed by SGA, VAS for appetite, albumin, and prealbumin. The performance status and quality of life were stable throughout the observation and were not changed under the supplementation., Competing Interests: None of the authors has a conflict of interest.

Neutropenia and febrile neutropenia (FN) are among the most common side effects/complications of chemotherapy. The aim of the present study was to evaluate the practice of the use of biosimilar filgrastim in the primary and secondary prevention of FN, and assess its efficacy and safety. A multi-center, non-interventional epidemiological study of 170 cancer patients aged 23-82 years was conducted. Data were collected via a questionnaire completed based on medical documentation and patient examination over five chemotherapy visits. The risk of FN related to the chemotherapy protocol used was in the range of 10-20% in >50% of the patients (53.5%) and a majority (74.7%) had additional FN risk factors. 60% of the patients received filgrastim as primary prevention of FN, and 40% received it as secondary prevention. In 40.6% of cases, six cycles of chemotherapy were used. More than 90% of patients continued chemotherapy according to the initial recommended dose. In majority of patients, no FN was observed following the final cycle of chemotherapy. Median neutrophil count at visit 1 was 2.2×103/µl and did not fall below that level. Majority of patients (>70%) performed self-injections of filgrastim, and 86.3% of patients were continuing therapy with this drug at the last visit. No treatment-related side effects were recorded. The use of biosimilar filgrastim in the primary and secondary prevention of FN allows to maintain initial chemotherapy dosage. Furthermore, the use of biosimilar filgrastim is safe and tolerable, and has a high acceptance by patients.

Aim of the Study: Cancer is usually associated with impaired nutritional status, which is one of the factors contributing to the deterioration of the results of surgery, chemotherapy, or radiotherapy. The aim of this study was the assessment of the nutritional status of patients with CRC qualified to chemotherapy., Material and Methods: Seventy-five persons aged 40-86 years with colorectal cancer were examined. To evaluate the nutritional status NRS 2002, SGA, SCRINIO Working Group classification, VAS scale for appetite, and FAACT questionnaire were used. The health status of patients was evaluated based on the Karnofsky Performance Scale. Anthropometric measurements were made., Results: The results indicate that 75% of patients present pre-cachexia status based on SCRINIO Working Group classification. According to both NRS-2002 and SGA, 73.3% of patients were moderately malnourished and 2.7% were severely malnourished. 37.0% of patients had moderate appetite and 6.0% ( n = 5) had poor appetite. The Karnofsky score indicates the state of normal activity, and minor signs and symptoms of the disease among most of the patients. A statistically significant positive correlation was found between the VAS and the Karnofsky score (R = 0,4; p < 0.05). The FACCT average score (78.5) indicates a reduction in the quality of life of the patients in all aspects of functioning., Conclusions: Evaluation of the baseline nutritional status of patients with CRC should be a part of routine clinical practice. Because of the high incidence of confirmed pre-cachexia, this group of patients also requires early adequate nutrition intervention., Competing Interests: The authors declare no conflict of interest.

Decreased level of L-arginine may lead to airway hyperresponsiveness, inflammation, and airway remodeling. Changes in L-arginine metabolism were observed earlier in adult asthmatic patients. Studies on L-arginine metabolism in children with bronchial asthma are limited. Because biosynthesis of L-arginine is insufficient in growing children, its potential metabolic alterations may have important clinical implications. This study was designed to evaluate L-arginine metabolism in children with well-controlled asthma. The studies were conducted on blood serum of 30 asthmatic and 20 healthy children (control group). Levels of L-arginine and its metabolic products, L-citrulline and L-ornithine, were measured by HPLC. Arginase activity was determined spectrophotometrically. Disease severity was evaluated by the asthma control test (ACT) and the level of nitric oxide (NO) in exhaled air. In asthmatic children L-arginine concentration was significantly lowered, whereas arginase activity was unchanged when compared with the healthy group. However, L-ornithine and L-citrulline levels were significantly increased. There was no correlation between arginase activity, amino acids levels, ACT scores, and exhaled NO. In children with chronic, well-controlled asthma L-arginine metabolism is altered. Given that L-arginine is absolutely essential for children, our findings may be of particular importance for the management of children with non-exacerbated asthma. They may also help to develop new therapeutic strategies targeted at L-arginine metabolism in the future.

Cancer, being in fact a generalized disease involving the whole organism, is most frequently associated with metabolic deregulation, a latent inflammatory state and anorexia of various degrees. The pathogenesis of this disorder is complex, with multiple dilemmas remaining unsolved. The clinical consequences of the above-mentioned disturbances include cancer-related cachexia and anorexia-cachexia syndrome. These complex clinical entities worsen the prognosis, and lead to deterioration of the quality of life and performance status, and thus require multimodal treatment. Optimal therapy should include nutritional support coupled with pharmacotherapy targeted at underlying pathomechanisms of cachexia. Nevertheless, many issues still need explanation, and efficacious and comprehensive therapy of cancer-related cachexia remains a future objective.