PURPOSE: While anal cancer is a very rare oncological diagnosis representing less than 2% of lower gastrointestinal tract cancers, the incidence has doubled in the past 20 years. Radical radiochemotherapy with sequential or simultaneous boost is now the standard treatment modality. Interstitial HDR brachytherapy is one of the boost application options. Implementation of new radiotherapy techniques has resulted in improved therapeutic outcomes; however, it is still associated with acute and especially late toxicity. Gastrointestinal disorders and sexual dysfunction are the most frequent factors affecting the long-term quality of cured patients' lives. METHODS: A total of 96 patients consecutively treated between 2000 and 2022 with external beam radio-/chemotherapy and an interstitial brachytherapy boost for histologically verified nonmetastatic anal squamous cell carcinoma were evaluated. The median follow-up time was 15.4 years (range 13.4-17.3 years). The primary objective of the study was to assess local control (LC) and quality of life (QoL). The Czech versions of internationally validated EORTC questionnaires were used to evaluate life quality-the basic EORTC QOL-C30 v.3 and the specific QOL-ANL 27 questionnaire. RESULTS: Local control was 85.5% at 5 years, 83.4% at 10 years, 83.4% at 15 years, and 83.4% at 20 years, and there was no dependence on clinical stage. The most common forms of acute toxicity were cutaneous and hematological but were gastrointestinal for late toxicities. In the evaluation of quality of life, 80.5% of patients alive at the time participated. In the EORTC quality of life questionnaire C30 v.3, patients rated the functional scale score as 86.2 points (standard deviation [SD] = 12.6) and the symptom score as 15.5 points (SD = 12.5). The global health score achieved 68.4 points (SD = 23.6). The most common symptoms were fatigue with 25.6 points (SD = 20.2) and diarrhea with 19.0 points (SD = 27.8). In the QOL-ANL 27 questionnaire, symptom scales assessing bowel symptoms were scored 27.5 points (SD = 19) in non-stoma patients and 11.9 points (SD = 17.2) in stoma patients. In the single-item symptom scales, the highest scores were rated for frequency of urination with 26.4 points (SD = 30.8), need to be close to a toilet with 22.4 points (SD = 27.3), and self-cleaning more often with 25.3 points (SD = 31.8). In the functional scales assessing sex life and interest, men and women reported scores of 45.2 (SD = 23) and 45.5 points (SD = 19), respectively. CONCLUSION: Boost with interstitial HDR brachytherapy is an established safe method of anal cancer treatment, with excellent results and limited late toxicity. Functioning scales were rated relatively highly in QoL questionnaires, and the overall global health score was comparable to published data. Gastrointestinal difficulties, fatigue, and sexual dysfunction dominated the symptom scales in our cohort.
- MeSH
- Brachytherapy * methods MeSH
- Radiotherapy Dosage MeSH
- Adult MeSH
- Quality of Life * psychology MeSH
- Middle Aged MeSH
- Humans MeSH
- Anus Neoplasms * radiotherapy psychology pathology MeSH
- Follow-Up Studies MeSH
- Surveys and Questionnaires MeSH
- Radiation Injuries * psychology etiology MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Carcinoma, Squamous Cell * radiotherapy pathology MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
One of the most common statistical analyses in experimental psychology concerns the comparison of two means using the frequentist t test. However, frequentist t tests do not quantify evidence and require various assumption tests. Recently, popularized Bayesian t tests do quantify evidence, but these were developed for scenarios where the two populations are assumed to have the same variance. As an alternative to both methods, we outline a comprehensive t test framework based on Bayesian model averaging. This new t test framework simultaneously takes into account models that assume equal and unequal variances, and models that use t-likelihoods to improve robustness to outliers. The resulting inference is based on a weighted average across the entire model ensemble, with higher weights assigned to models that predicted the observed data well. This new t test framework provides an integrated approach to assumption checks and inference by applying a series of pertinent models to the data simultaneously rather than sequentially. The integrated Bayesian model-averaged t tests achieve robustness without having to commit to a single model following a series of assumption checks. To facilitate practical applications, we provide user-friendly implementations in JASP and via the RoBTT package in R . A tutorial video is available at https://www.youtube.com/watch?v=EcuzGTIcorQ.
- MeSH
- Bayes Theorem MeSH
- Psychology, Experimental * methods MeSH
- Data Interpretation, Statistical MeSH
- Humans MeSH
- Models, Statistical * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Cervical cancer (CC) is the fourth most common malignant tumor in women worldwide. Detecting different biomarkers together on single cells by novel method mass cytometry could contribute to more precise screening. Liquid-based cytology (LBC) cervical samples were collected (N = 53) from women categorized as normal and precancerous lesions. Human papillomavirus was genotyped by polymerase chain reaction, while simultaneous examination of the expression of 29 proteins was done by mass cytometry (CyTOF). Differences in cluster abundances were assessed with Spearman's rank correlation as well as high dimensional data analysis (t-SNE, FlowSOM). Cytokeratin (ITGA6, Ck5, Ck10/13, Ck14, Ck7) expression patterns allowed determining the presence of different cells in the cervical epithelium. FlowSOM analysis enabled to phenotype cervical cells in five different metaclusters and find new markers that could be important in CC screening. The markers Ck18, Ck18, and CD63 (Metacluster 3) showed significantly increasing associated with severity of the precancerous lesions (Spearman rank correlation rho 0.304, p = 0.0271), while CD71, KLF4, LRIG1, E-cadherin, Nanog and p53 (Metacluster 1) decreased with severity of the precancerous lesions (Spearman rank correlation rho -0.401, p = 0.0029). Other metaclusters did not show significant correlation, but metacluster 2 (Ck17, MCM, MMP7, CD29, E-cadherin, Nanog, p53) showed higher abundance in low- and high-grade intraepithelial lesion cases. CyTOF appears feasible and should be considered when examining novel biomarkers on cervical LBC samples. This study enabled us to characterize different cells in the cervical epithelium and find markers and populations that could distinguish precancerous lesions.
- MeSH
- Cervix Uteri pathology metabolism MeSH
- Adult MeSH
- Uterine Cervical Dysplasia diagnosis pathology MeSH
- Papillomavirus Infections pathology diagnosis virology MeSH
- Kruppel-Like Factor 4 * MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor * genetics metabolism MeSH
- Uterine Cervical Neoplasms * diagnosis pathology genetics MeSH
- Precancerous Conditions * pathology diagnosis MeSH
- Flow Cytometry * methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Crystalloid and colloid solutions commonly used in intensive and perioperative care can affect haemocoagulation status. This in vitro study assessed the impact of Plasma-Lyte, albunorm 5%, and Gelaspan 4% solutions on primary and secondary haemostasis using rotational thromboelastometry and platelet function analyser. METHODS: In this prospective study, we examined blood samples from 20 healthy volunteers using rotational thromboelastometry and platelet function analyser. Simultaneously, we analysed the blood samples subjected to 10% dilution using Plasma-Lyte, albunorm 5%, and Gelaspan 4% solutions. RESULTS: Compared to controls, Plasma-Lyte shortened EXTEM-CT (p = 0.005) and reduced FIBTEM-MCF (p = 0.017). albunorm 5% prolonged EXTEM-CFT (p = 0.001), decreased EXTEM-alpha (p < 0.001) and MCF in EXTEM, INTEM, and FIBTEM tests (p < 0.001, p = 0.038, p = 0.001, respectively), along with MCE in the PLTEM test (p < 0.001). Gelaspan 4% also prolonged EXTEM-CFT (p < 0.001), decreased EXTEM-alpha (p < 0.001) and MCF in EXTEM, INTEM, and FIBTEM tests (p < 0.001, p < 0.001, p = 0.009, respectively), along with MCE in the PLTEM test (p < 0.001). Gelaspan 4% also reduced EXTEM-CT (p = 0.021). All solution prolonged CT in PFA Col/ADP (p = 0.003 for Plasma-Lyte, p < 0.001 for albunorm and Gelaspan) and albunorm 5% also prolonged CT in Col/Epi (p = 0.003). CONCLUSION: Plasma-Lyte had the least effect on secondary haemostasis, whereas albunorm 5% had the least effect among colloids. Gelaspan 4% adversely affected the propagation phase of coagulation, maximal strength and elasticity of the coagulum, and the level of functional fibrinogen. All solutions adversely affected platelet function in primary haemostasis, with Plasma-Lyte showing the least effect.
- Publication type
- Journal Article MeSH
Cancer is a heterogeneous disease, which contributes to its rapid progression and therapeutic failure. Besides interpatient tumor heterogeneity, tumors within a single patient can present with a heterogeneous mix of genetically and phenotypically distinct subclones. These unique subclones can significantly impact the traits of cancer. With the plasticity that intratumoral heterogeneity provides, cancers can easily adapt to changes in their microenvironment and therapeutic exposure. Indeed, tumor cells dynamically shift between a more differentiated, rapidly proliferating state with limited tumorigenic potential and a cancer stem cell (CSC)-like state that resembles undifferentiated cellular precursors and is associated with high tumorigenicity. In this context, CSCs are functionally located at the apex of the tumor hierarchy, contributing to the initiation, maintenance, and progression of tumors, as they also represent the subpopulation of tumor cells most resistant to conventional anti-cancer therapies. Although the CSC model is well established, it is constantly evolving and being reshaped by advancing knowledge on the roles of CSCs in different cancer types. Here, we review the current evidence of how CSCs play a pivotal role in providing the many traits of aggressive tumors while simultaneously evading immunosurveillance and anti-cancer therapy in several cancer types. We discuss the key traits and characteristics of CSCs to provide updated insights into CSC biology and highlight its implications for therapeutic development and improved treatment of aggressive cancers.
- MeSH
- Humans MeSH
- Neoplastic Stem Cells * pathology metabolism MeSH
- Tumor Microenvironment * MeSH
- Neoplasms * pathology genetics metabolism therapy MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
INTRODUCTION: The objective of this study was to assess the impact of the Enhanced Recovery After Surgery (ERAS) programme implementation on treatment costs at a university-type centre, using the DRG scheme. MATERIALS AND METHODS: Retrospective analysis of patients' data in a group of 604 individuals enroled in the study. We evaluated three groups of patients according to the ERAS clinical protocol (CP): (1) CP oncogynaecology, (2) CP simple hysterectomy, (3) CP laparoscopy. The study aimed to evaluate the impact on the length of stay (LOS), savings in bed-days, and the reduction in direct treatment costs. Three parameters-antibiotic consumption, blood derivative consumption and laboratory test costs-were chosen to compare direct treatment costs. The statistical significance of the difference in the observed parameters was tested by a two-sample unpaired t test with unequal variances at the 0.05 significance level. RESULTS: We analysed data from 604 patients. In all three groups, the length of stay (LOS) was significantly reduced. The most significant reduction was observed in the CP oncogynaecology group, where the LOS was reduced from 11.1 days to 6.8 days (2022) and 7.6 days (2023) compared to 2019 (p < 0.05). Furthermore, there was a notable reduction in inpatient bed-days, which resulted in the capacity being made available to admit additional patients. A statistically significant reduction in direct costs was observed in the group of CP hysterectomy (antibiotic use) and in the CP laparoscopy (laboratory test costs). CONCLUSIONS: The implementation of the ERAS principles resulted in a number of significant positive economic impacts-reduction in the LOS and a corresponding increase in bed capacity for new patients. Additionally, direct treatment costs, including those related to antibiotic use or laboratory testing were reduced. The Czech Republic's acute healthcare system, like the majority of European healthcare systems, is financed by the DRG system. This flat-rate payment per patient encourages hospital management to seek cost-reduction strategies. The results of our study indicate that fast-track protocols represent a potential viable approach to reducing the cost of treatment while simultaneously meeting the recommendations of evidence-based medicine.
- MeSH
- Length of Stay statistics & numerical data economics MeSH
- Adult MeSH
- Gynecologic Surgical Procedures * economics MeSH
- Hysterectomy economics MeSH
- Diagnosis-Related Groups MeSH
- Laparoscopy economics MeSH
- Middle Aged MeSH
- Humans MeSH
- Health Care Costs * statistics & numerical data MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Enhanced Recovery After Surgery * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Mnohočetný myelom je druhým nejčastějším nádorovým onemocněním krve v České republice a jeho incidence stále stoupá. Ze zkušeností z každodenní klinické praxe vyplývá, že až polovina pacientů s mnohočetným myelomem se začíná léčit pozdě v důsledku pozdního stanovení diagnózy. Na zlepšení této skutečnosti byl zaměřen již původní projekt CRAB České myelomové skupiny. Aktuální článek shrnuje výsledky dotazníkové části projektu CRAB II, na kterou by měla navázat rozsáhlá informační kampaň o příznacích nemoci včetně doporučeného vyšetřovacího postupu při podezření na jejich možnou souvislost s tímto závažným onemocněním. Zlepšení diagnostiky mnohočetného myelomu, zejména co se týče časného stanovení diagnózy, a posun moderních léčebných postupů do první léčebné linie by měly do budoucna vést k dalšímu prodloužení a současně zlepšení kvality života nemocných.
Multiple myeloma is the second most common hematologic malignancy in the Czech Republic, and its incidence continues to rise. Clinical experience shows that up to half of patients with multiple myeloma begin treatment late due to delayed diagnosis. The original CRAB project by the Czech Myeloma Group was aimed at addressing this issue. The current article summarizes the results of the questionnaire phase of the CRAB II project, which is intended to be followed by a large-scale information campaign about the symptoms of the disease, including recommended diagnostic procedures when a possible connection to this serious condition is suspected. Improving the diagnosis of multiple myeloma – especially in terms of early detection – and advancing modern treatment approaches to first-line therapy should, in the future, lead to further prolongation and simultaneous improvement of patients’ quality of life.
Práce se zabývá využitím algoritmů umělé inteligence (artificial intelligence – AI) v diagnostice karcinomu prsu, plic a prostaty. Popisuje historický vývoj digitalizace patologických procesů, implementaci umělé inteligence a její současné aplikace v patologii. Zaměřuje se na strojové a hluboké učení, počítačové vidění a digitální patologii, které přispívají k automatizaci a zpřesnění diagnostiky. Důraz je kladen na konkrétní nástroje, jako jsou systémy uPath od Roche a IBEX Medical Analytics, které umožňují analýzu histopatologických snímků, klasifikaci nádorových buněk a hodnocení biomarkerů. Práce také reflektuje výhody využití AI, včetně zvýšení přesnosti diagnostiky a efektivity laboratorních procesů, ale zároveň upozorňuje na výzvy spojené s její implementací, jako jsou etické a právní aspekty, ochrana osobních údajů a odpovědnost za chyby. Cílem práce je poskytnout komplexní přehled o možnostech využití AI v digitální patologii a její roli v moderní onkologické diagnostice.
The study focuses on the utilization of artificial intelligence (AI) algorithms in the diagnosis of breast, lung, and prostate cancer. It describes the historical development of the digitalization of pathological processes, the implementation of artificial intelligence, and its current applications in pathology. The study emphasizes machine learning, deep learning, computer vision, and digital pathology, which contribute to the automation and refinement of diagnostics. Special attention is given to specific tools such as the uPath systems from Roche and IBEX Medical Analytics, which enable the analysis of histopathological images, tumor cell classification, and biomarker evaluation. The study also highlights the benefits of AI utilization, including increased diagnostic accuracy and efficiency in laboratory processes, while simultaneously addressing the challenges associated with its implementation, such as ethical and legal considerations, data protection, and liability for errors. The aim of this study is to provide a comprehensive overview of the potential applications of AI in digital pathology and its role in modern oncological diagnostics.
In the study, we employ an affordable, tissue-saving, and precise simultaneous multiplex immunofluorescence method with heat-induced antibody stripping to identify and structurally analyse nigral Lewy bodies in dopaminergic neurones. Analysis of different alpha-synuclein epitopes and proteoforms reveals an almost uniform, onion-like morphology of the Lewy bodies. The N-terminal and C-terminal domains are predominantly accessible to antibody binding in the peripheral shell of the bodies.
- MeSH
- alpha-Synuclein * metabolism analysis MeSH
- Lewy Body Disease pathology MeSH
- Dopaminergic Neurons metabolism pathology MeSH
- Fluorescent Antibody Technique methods MeSH
- Lewy Bodies * metabolism pathology MeSH
- Humans MeSH
- Substantia Nigra * metabolism pathology MeSH
- Hot Temperature MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Fever is associated with brain injury after cardiac arrest. It is unknown whether fever management with a feedback-controlled device impacts patient-centered outcomes in cardiac arrest patients. This trial aims to investigate fever management with or without a temperature control device after out-of-hospital cardiac arrest. METHODS: The TEMP-CARE trial is part of the 2 × 2 × 2 factorial Sedation, TEmperature and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial, a randomized, international, multicenter, parallel-group, investigator-initiated, superiority trial that will evaluate sedation strategies, temperature management, and blood pressure targets simultaneously in nontraumatic/nonhemorrhagic out-of-hospital cardiac arrest patients following hospital admission. For the temperature management component of the trial described in this protocol, patients will be randomly allocated to fever management with or without a feedback-controlled temperature control device. For those managed with a device, if temperature ≥37.8°C occurs within 72 h post-randomization the device will be started targeting a temperature of ≤37.5°C. Standard fever treatment, as recommended by local guidelines, including pharmacological agents, will be provided to participants in both groups. The two other components of the STEPCARE trial evaluate sedation and blood pressure strategies. Apart from the STEPCARE trial interventions, all other aspects of general intensive care will be according to the local practices of the participating site. A physician blinded to the intervention will determine the neurological prognosis following European Resuscitation Council and European Society of Intensive Care Medicine guidelines. The primary outcome is all-cause mortality at six months post-randomization. To detect a 5.6% absolute risk reduction (90% power, alpha .05), 3500 participants will be enrolled. Secondary outcomes include poor functional outcome at six months, intensive care-related serious adverse events, and overall health status at six months. CONCLUSION: The TEMP-CARE trial will investigate if post-cardiac arrest management of fever with or without a temperature control device affects patient-important outcomes after cardiac arrest.
- MeSH
- Fever * therapy MeSH
- Cardiopulmonary Resuscitation * MeSH
- Humans MeSH
- Multicenter Studies as Topic MeSH
- Randomized Controlled Trials as Topic MeSH
- Body Temperature MeSH
- Hypothermia, Induced * instrumentation MeSH
- Out-of-Hospital Cardiac Arrest * therapy complications MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial Protocol MeSH
