INTRODUCTION: In developed countries, urologic fistulas arise mainly from malignancies, radiotherapy, or surgical trauma. Hysterectomy and radiation therapy are both critical components of the treatment of women with cancers. Urologic fistulas significantly reduce the quality of life of cancer patients, and may result in delays or even refusal of adjuvant treatment by these patients, thereby negatively impacting both short- and long-term cancer survival. MATERIALS AND METHODS: A 10-year retrospective study of urologic fistulas associated with gynaecologic malignancies at the University hospital Hradec Kralove, Czech Republic was conducted. Descriptive statistics of the fistula and treatment characteristics of women with malignant fistulas were conducted using the NCSS 22 statistical software program (NCSS, Keysville, Utah). RESULTS: Cervical cancer was mostly commonly associated with urologic fistulas (36, 76.8%). Most of the malignant fistulas were complex (41, 87.2%) vesicovaginal (23, 48.9%) fistulas (VVFs). More than two-thirds (33, 70.2%) of the fistulas were diagnosed following radiotherapy, with a time interval from radiotherapy to fistula diagnosis of between 3.00 and 14.50 years. Primary fistuloraphy was performed for all the six cases with simple VVFs and seven (41.2%) of the 17 patients with complex VVFs. Treatment success rate was 83.33% and 14.3% for simple and complex fistulas, respectively. All the failed complex fistula repairs recurred. CONCLUSION: Malignant fistulas predominantly follow radiotherapy for cervical cancers, and are usually detected up to 15 years post-radiotherapy. Most are complex VVFs, which are difficult to treat, with a high rate of recurrence.
- MeSH
- Adult MeSH
- Hysterectomy adverse effects MeSH
- Quality of Life MeSH
- Middle Aged MeSH
- Humans MeSH
- Urinary Fistula * etiology epidemiology MeSH
- Uterine Cervical Neoplasms * complications MeSH
- Genital Neoplasms, Female * complications therapy pathology MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Vesicovaginal Fistula * etiology epidemiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Immune checkpoints are critical in modulating immune responses and maintaining self-tolerance. Cancer cells can exploit these mechanisms to evade immune detection, making immune checkpoints attractive targets for cancer therapy. The introduction of immune checkpoint inhibitors (ICIs) has transformed cancer treatment, with monoclonal antibodies targeting CTLA-4, PD-1, and PD-L1 demonstrating clinical success. However, challenges such as immune-related adverse events, primary and acquired resistance, and high treatment costs persist. To address these challenges, it is essential to explore alternative strategies, including small-molecule and peptide-based inhibitors, aptamers, RNA-based therapies, gene-editing technologies, bispecific and multispecific agents, and cell-based therapies. Additionally, innovative approaches such as lysosome-targeting chimeras, proteolysis-targeting chimeras, and N-(2-hydroxypropyl) methacrylamide copolymers are emerging as promising options for enhancing treatment effectiveness. This review highlights significant advancements in the field, focusing on their clinical implications and successes.
Host infectiousness to insect vectors is a crucial parameter for understanding the transmission dynamics of insect-borne infectious diseases such as leishmaniases. Despite their importance, critical factors influencing the outwards transmission of Leishmania major, including parasite distribution within the host body and the minimum number of skin amastigotes required for vector infection, remain poorly characterized. To address these gaps, we studied these parameters in the natural North African reservoir host Meriones shawi and in BALB/c mice infected with a low parasite dose. Using qPCR, we quantified Leishmania loads in different zones (regions) of infected ear pinnae, whereas microscale infectiousness was evaluated via microbiopsies and fluorescence microscopy. The amastigote distribution within infected ears was heterogeneous, with pronounced differences between the lesion center, lesion margin, and visually unaffected surrounding skin. Phlebotomus papatasi females that fed in areas where no amastigotes were detected via microscopy did not become infected. In M. shawi, lesion margins have emerged as the most effective source of infection. The number of amastigotes at bite sites where sand fly females became infected ranged from 4--500, with as few as 2--10 amastigotes sufficient to initiate vector infection. This low infection threshold was confirmed by experiments in which P. papatasi was fed through a chick-skin membrane. In contrast, the BALB/c mouse model showed only minor differences in infectiousness between lesion centers and margins. The minimum infectious dose in BALB/c mice was approximately 100 times greater than that in M. shawi, with successful infections occurring at sites containing 1,500-10,000 amastigotes. These findings advance our understanding of Leishmania transmission by addressing critical knowledge gaps and enabling more accurate modelling of cutaneous leishmaniasis epidemiology. Moreover, this study highlights the importance of incorporating natural host models in research, as the dynamics of disease progression and transmission parameters can differ significantly between natural hosts and standard laboratory models.
- MeSH
- Gerbillinae * parasitology MeSH
- Insect Vectors * parasitology MeSH
- Skin parasitology MeSH
- Leishmania major * physiology pathogenicity MeSH
- Leishmaniasis, Cutaneous * transmission parasitology MeSH
- Disease Models, Animal MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Parasite Load MeSH
- Phlebotomus * parasitology MeSH
- Disease Reservoirs * parasitology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The key viral protein for infection by SARS-CoV-2 is the spike glycoprotein (S protein), mediating entry into host cells, which therefore represents a strong focus for the development of targeted therapeutics. In this work, we explored the fatty acid binding pocket within the S protein, which stabilizes an inactive conformation and disrupts cell recognition and infection. To explore the potential of this site as a drug target, molecular dynamics simulations were performed, followed by a docking-based virtual screening of commercial druglike compounds. This in silico procedure enabled the identification of potential inhibitors of SARS-CoV-2 cell infection, likely by stabilizing an inactive spike conformation, detected in binding assays, although further experiments are required to directly confirm this action. The antiviral effect of the virtual hits was analyzed in cell-based assays, and one molecule displayed a low micromolar activity. Starting from the best antiviral compound found, structural analogues were purchased and evaluated in antiviral assays. An increase in activity was observed for multiple analogues, with the strongest antiviral compound showing submicromolar activity and low cytotoxicity. The successful identification of a new antiviral scaffold through in silico studies might pave the way for the further development of antivirals against SARS-CoV-2 and shows the reliability of the methodologies applied.
- Publication type
- Journal Article MeSH
Úvod: Onkologické skríningy sú kľúčové pre včasné odhalenie rakoviny a zvýšenie šancí na úspešnú liečbu. Sestry hrajú dôležitú rolu v edukácii pacientov a verejnosti o prevencii onkologických ochorení. Cieľ: Cieľom prieskumu bolo zistiť úroveň vedomostí študentov ošetrovateľstva o onkologických skríningových programoch na Slovensku. Metodika: Prieskum sa uskutočnil na Fakulte ošetrovateľstva a zdravotníckych odborných štúdií Slovenskej zdravotníckej univerzity v Bratislave od novembra 2023 do februára 2024. Prieskumná vzorka zahŕňala denných študentov bakalárskeho štúdia ošetrovateľstva, ktorí vyplnili dotazník zameraný na onkologické skríningové programy na Slovensku. Dotazník obsahoval 4 sociodemografické, 14 vedomostných a 2 osobnostné otázky. Prieskum bol dobrovoľný, anonymný a vyžadoval súhlas študenta. Výsledky boli vyhodnotené v absolútnych a relatívnych číslach. Výsledky: Prieskumu sa zúčastnilo 129 študentov (100 %), z toho 124 (96,12 %) žien a 5 (3,88 %) mužov. Najväčšiu skupinu tvorili študenti 1. ročníka v počte 58 (44,97 %). Priemerný počet získaných bodov bol 9,7 z maximálnych 14 bodov (min. 2, max. 14, SD: 3,4), čo predstavuje 69,73% úspešnosť vo vedomostných otázkach. Najvyššiu úspešnosť dosiahli študenti 3. ročníka (74 %). Najlepšie výsledky dosiahli študenti v odpovediach týkajúcich sa rakoviny krčka maternice (61 – 85 % správnych odpovedí), zatiaľ čo najnižšie výsledky pri otázkach o rakovine prsníka (24 – 65 % správnych odpovedí). Až 97,67 % študentov vyjadrilo záujem dozvedieť sa viac o prevencii v onkológii, pričom 62,79 % študentov sa domnieva, že by nedokázali edukovať pacienta v oblasti onkologickej prevencie. Záver: Vzhľadom na rastúcu incidenciu onkologických ochorení je dôležité zamerať sa na vzdelávanie študentov ošetrovateľstva v oblasti prevencie v onkológii, aby boli pripravení vykonávať edukačné intervencie a zvyšovať zdravotnú gramotnosť pacientov a širokej verejnosti.
Introduction: Cancer screenings are essential for the early detection of cancer and increasing the chances of successful treatment. Nurses play a crucial role in educating patients and the public about cancer prevention. Aim: The aim of the survey was to assess nursing students’ knowledge of cancer screening programs in Slovakia. Methodology: The survey was conducted at the Faculty of Nursing and Professional Health Studies of the Slovak Medical University in Bratislava from November 2023 to February 2024. The survey sample included full-time bachelor’s nursing students who completed a questionnaire focused on cancer screening programs in Slovakia. The questionnaire consisted of 4 sociodemographic, 14 knowledgebased, and 2 personal questions. Knowledge-based questions were evaluated, for which students could earn a maximum of 14 points. The student received 1 point for each correct answer, and for an incorrect answer or no answer, they received 0 points. Participation in the survey was voluntary, anonymous, and required the student’s consent. The results were evaluated in absolute and relative numbers. Results: A total of 129 students (100%) participated in the survey, including 124 women (96.12%) and 5 men (3.88%). The largest group consisted of first-year students, with 58 participants (44.97%). The average number of points obtained was 9.7 out of a maximum of 14 (min:. 2, max. 14, SD: 3.4), representing a 69.73% success rate in knowledge-based questions. The highest success rate was achieved by third-year students (74%). The best results were obtained in questions related to cervical cancer (61–85% correct answers), while the lowest results were observed in questions about breast cancer (24–65% correct answers). As many as 97.67% of students expressed interest in learning more about cancer prevention, while 62.79% believed they would not be able to educate a patient about cancer prevention. Conclusion: Given the increasing incidence of cancer diseases, it is crucial to focus on educating nursing students in cancer prevention to prepare them for providing educational interventions and enhancing the health literacy of patients and the general public.
Cardiovascular disease (CVD) is a leading cause of death worldwide. A key area of interest in CVD prevention is novel digital health technologies, primarily mobile health (mHealth) applications and wearable devices, that are rapidly transforming the methods of preventing and managing CVD. Studies have shown the success of smartphone applications, such as the RITMIA app (Heart SentinelTM, Parma, Italy), in successfully detecting atrial fibrillation (Afib) compared to a classic 12-lead electrocardiogram (ECG). mHealth devices should integrate these factors, based on artificial intelligence (AI) and driven by chatbots, to encourage patients to use technology through interactive, real-world, motivational, and timely feedback. Data from mHealth clinical research indicate improved medication adherence, weight control, and self-care among patients. This review highlights mHealth and wearable devices in CVD prevention, providing foresight into cardiovascular health conditions through continuous monitoring, early detection, and improved patient engagement. Additionally, it examines challenges, including ethical, regulatory, and accessibility issues, that need to be addressed before their widespread adoption. In the future, the priority must be integration with healthcare systems and equitable access. A thorough search was conducted using reputable databases such as Scopus, PubMed, and Google Scholar. Articles from 2015 to 2025, along with an article from 2002 published in reputable peer-reviewed journals, were analyzed and contextually used. We also refined our search terms and used high-quality English articles to achieve this.
- Publication type
- Journal Article MeSH
- Review MeSH
Úvod: Nehmatné léze prsu, u kterých je možný prs záchovný chirurgický výkon, vyžadují přesná předoperační označení patologického ložiska. Mamografický screening a moderní diagnostické metody vedou k stále časnější detekci těchto lézí. Metody: Představujeme naše 2leté praktické zkušenosti se značením nehmatných lézí radioaktivním zrnem Advantage™ I-125. Tuto metodu jsme aplikovali u 116 pacientek, z toho 34 pacientek bylo po úspěšné neoadjuvantní systémové terapii. Prvních 13 pacientek jsme značili duplicitně metodou Frankova vodiče spolu s aplikací zrna. Cílem naší práce bylo zhodnotit výhody a nevýhody metody jak pro pacientky, tak pro celý multidisciplinární tým. Výsledky: Úspěšně jsme odstranili všechna patologická ložiska během primárního výkonu. U 4 pacientek jsme zaznamenali dislokaci zrna, přičemž vždy došlo k identifikaci patologického ložiska i zrna v operačním poli. Z celkového počtu pacientek bylo 73 pacientek operováno pro duktální karcinom, 20 pacientek pro lobulární karcinom, 8 pacientek pro karcinom v terénu mikrokalcifikací, 2 pacientky pro invazivní papilární karcinom a 13 pacientek pro nejednoznačný bioptický nález. Metoda umožňuje přesné zaměření nehmatných lézí s minimální radiační zátěží pro pacientky i operační tým. Rovněž kosmetické výsledky této metody hodnotíme jednoznačně pozitivně. Závěr: Radioaktivní značení zrnem Advantage™ I-125 se nám potvrdilo jako spolehlivá metoda pro detekci nehmatných lézí prsu s minimálními komplikacemi. Její výhodu spatřujeme především v celkovém komfortu pro pacientky a z estetického hlediska nám umožňuje optimální umístění řezu. Naše výsledky potvrzují vysokou efektivitu této metody v rámci prs záchovného výkonu s dosažením R0 resekce.
Introduction: Non-palpable breast lesions that are eligible for breast-conserving surgery require precise preoperative localization of the pathological site. Mammographic screening and modern diagnostic methods contribute to the increasingly early detection of these lesions. Methods: We present our two-year practical experience with the marking of non-palpable breast lesions using the Advantage™ I-125 radioactive seed. This method was applied to 116 patients, 34 of whom had undergone successful neoadjuvant systemic therapy. The first 13 patients were marked using both the Frank wire method and radioactive seed application. The aim of our study was to evaluate the advantages and disadvantages of this method for both the patients and the entire multidisciplinary team. Results: All pathological lesions were successfully removed during the primary procedure. In four patients, we observed seed displacement; however, the pathological lesion and the seed were always identified within the surgical field. Among the total number of patients, 73 underwent surgery for ductal carcinoma, 20 for lobular carcinoma, 8 for carcinoma associated with microcalcifications, 2 for invasive papillary carcinoma, and 13 for ambiguous biopsy findings. The method enables precise targeting of non-palpable lesions with minimal radiation exposure for both the patients and the surgical team. Additionally, the cosmetic outcomes of this method were assessed as clearly positive. Conclusion: The Advantage™ I-125 radioactive seed localization proved to be a reliable method for detecting non-palpable breast lesions with minimal complications. Its main advantages lie in the overall comfort for patients and the ability to optimize incision placement from an aesthetic perspective. Our results confirm the high effectiveness of this method in breast-conserving surgery while achieving R0 resection.
- Keywords
- nehmatné léze prsu, radioaktivní zrno,
- MeSH
- Staining and Labeling methods instrumentation MeSH
- Surgical Procedures, Operative methods statistics & numerical data MeSH
- Isotope Labeling * methods instrumentation MeSH
- Organ Sparing Treatments methods instrumentation MeSH
- Humans MeSH
- Breast Neoplasms * surgery diagnostic imaging pathology MeSH
- Preoperative Care methods instrumentation MeSH
- Breast surgery diagnostic imaging pathology MeSH
- Radioactive Tracers MeSH
- Iodine Radioisotopes therapeutic use MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Clinical Study MeSH
INTRODUCTION: Pulsed Field Cryoablation (PFCA) is a dual-energy cardiac ablation modality consisting of short-duration ultra-low temperature cryoablation (ULTC) followed immediately by pulsed field ablation (PFA) delivered from the same catheter. It is hypothesized that PFCA may improve contact stability during PFA, while maintaining lesion depth and effectiveness of ULTC. METHODS: PARALELL is a first-in-human multicenter study evaluating safety and effectiveness of a novel PFCA catheter and system in patients with persistent atrial fibrillation (PsAF) using the combination of pulmonary vein (PVI) and posterior wall (PWI) isolation. RESULTS: Sixty-six patients were ablated at six sites. One groin hematoma and one intubation-related hospitalization were the only serious procedure- or device-related adverse events recorded in the study. Per protocol, acute effectiveness was evaluated in 46 patients, including 31 patients with post-hoc analysis of cryogenic energy per lesion. After an average of 21.1 ± 9.3 lesions per patient the rates of PVI and PWI were 95.7% (176/184) and 97.7% (42/43), respectively. The average cryogenic energy per patient was highly predictive of acute isolation success with ROC AUC = 0.944% and 100% rates of both PVI and PWI in 24 patients in the optimal energy cohort. Grade I microbubbles and faint muscle contractions were detected in 1.1% and 0.5% of ablations, respectively. CONCLUSION: This initial multi-center experience suggests that PFCA can be efficiently performed for PVI and PWI using a single versatile catheter system, with high acute success and good early safety profile. The evaluation of the chronic 12-month effectiveness of PFCA is ongoing.
- MeSH
- Action Potentials MeSH
- Time Factors MeSH
- Equipment Design MeSH
- Atrial Fibrillation * surgery physiopathology diagnosis MeSH
- Cryosurgery * adverse effects instrumentation methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Risk Factors MeSH
- Aged MeSH
- Heart Rate MeSH
- Cardiac Catheters MeSH
- Pulmonary Veins * surgery physiopathology MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Multicenter Study MeSH
BACKGROUND: This study aimed to evaluate the effectiveness of different tracers ́ application techniques for sentinel lymph node (SLN) detection in women with endometrial cancer undergoing laparotomy. Additionally, potential risk factors for SLN detection failure were assessed. METHODS: We retrospectively analyzed data from 248 endometrial cancer patients who underwent abdominal surgery with SLN mapping between January 2020 and March 2024. Statistical analyses were conducted using the Wilcoxon rank sum test for continuous variables and either Pearson's chi-square test or Fisher's exact test for categorical variables, with a significance level set at p < 0.05. RESULTS: Group I + S consisted of 147 women with intracervical and subserosal tracers ́application and group I + I included 101 women with intracervical and intrafundal application. Successful detection of SLN on both sides was achieved in 39.9% (99/248) of all patients, in 38.1% (56/147) in the I + S group and in 42.6% (43/101) in the I + I group, respectively. SLNs were identified in 32.7% (81/248) of all patients on only one side of the pelvis, in 31.3% (46/147) in the I + S and in 34.7% (35/101) in the I + I group, respectively. No SLNs were detected in 27.4% (68/248) of all subjects, comprising 30.6% (45/147) from the I + S and 22.8% (23/101) from the I + I group. Although the success rate of SLN detection was higher in the I + I group and on the right side of the pelvis regardless of the detection method, these differences were not statistically significant. An age exceeding 66.3 years was recognized as a critical risk factor for successful detection, other followed factors did not demonstrate a statistically significant impact on overall detection success. Additional significant risk factors were identified: depth of tumor myometrial invasion on the right side, history of pelvic surgery, and total tumor volume on the left side. CONCLUSIONS: The study did not reveal significant differences in SLN mapping success between the groups receiving intracervical + intrafundal and intracervical + subserosal tracers ́applications among endometrial cancer patients treated via open surgery. Overall, older age emerged as the most critical risk factor for SLN detection failure, while other assessed factors did not show a statistically significant impact on overall detection success. TRIAL REGISTRATION: Institution University Hospital Královské Vinohrady, Prague, Czech Republic. REGISTRATION NUMBER: EK-VP-21-0-2023. Date of registration 7-JUN-2023. This study was retrospectively registered in compliance with the Declaration of Helsinki.
- MeSH
- Sentinel Lymph Node Biopsy * methods MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphatic Metastasis MeSH
- Endometrial Neoplasms * surgery pathology MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sentinel Lymph Node * pathology diagnostic imaging surgery MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
Early detection of type 1 diabetes, in its presymptomatic stage, offers significant clinical advantages, including treatment that can delay disease onset. Current screening focuses on identifying islet autoantibody positivity, with proposed optimal testing at ages 2, 6 and 10 years potentially achieving up to 80% sensitivity. However, challenges arise from participation rates and costs associated with multiple screenings. Genetic pre-screening has been suggested as a complementary strategy to target high-risk individuals prior to autoantibody testing, but its real-world benefits remain uncertain. Broad genetic selection strategies, based on family history, HLA typing or polygenic risk scores, can identify subsets of the population at elevated risk. However, these approaches face issues like low recall rates, socioeconomic biases and limited applicability across diverse ancestries. Additionally, the cost-effectiveness and infrastructure requirements of integrating genetic testing into routine healthcare remain significant hurdles. The combined use of genetic and autoantibody testing could improve predictive value, especially with innovations like point-of-care genetic testing. Yet, the ultimate success of any screening programme depends less on specific strategies and more on maximising public and healthcare-provider engagement, ensuring high participation, and addressing socioeconomic and demographic disparities. Digital-health infrastructure may play a crucial role in improving recall rates and maintaining follow-up adherence. In conclusion, while repeated islet autoantibody screening remains the most effective standalone approach, conducting genetic screening prior to islet autoantibody testing may be practical in certain contexts, provided that sufficient resources and equitable strategies are employed. Public engagement and robust infrastructure are essential to realising the full potential of early type 1 diabetes detection programmes.
- MeSH
- Autoantibodies * immunology MeSH
- Diabetes Mellitus, Type 1 * diagnosis genetics immunology MeSH
- Genetic Testing * methods MeSH
- Islets of Langerhans * immunology MeSH
- Humans MeSH
- Mass Screening methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
