Network analysis of England's single parent household COVID-19 control policy impact: a proof-of-concept study.

Lockdowns have been a core infection control measure in many countries during the coronavirus disease 2019 (COVID-19) pandemic. In England's first lockdown, children of single parent households (SPHs) were permitted to move between parental homes. By the second lockdown, SPH support bubbles between households were also permitted, enabling larger within-household networks. We investigated the combined impact of these approaches on household transmission dynamics, to inform policymaking for control and support mechanisms in a respiratory pandemic context. This network modelling study applied percolation theory to a base model of SPHs constructed using population survey estimates of SPH family size. To explore putative impact, varying estimates were applied regarding extent of bubbling and proportion of different-parentage within SPHs (DSPHs) (in which children do not share both the same parents). Results indicate that the formation of giant components (in which COVID-19 household transmission accelerates) are more contingent on DSPHs than on formation of bubbles between SPHs, and that bubbling with another SPH will accelerate giant component formation where one or both are DSPHs. Public health guidance should include supportive measures that mitigate the increased transmission risk afforded by support bubbling among DSPHs. Future network, mathematical and epidemiological studies should examine both independent and combined impact of policies.

[Immunotherapy of Colorectal and Anal Carcinoma]. / Imunoterapie nádoru dolní cásti trávicí trubice.

BACKGROUND: The lower part of the digestive tract includes the large intestine, rectum and anus. Treatment algorithms of cancers in these localities have significant differences in both early and advanced stages. The vast majority of metastatic cases are incurable. A few years ago, it was generally accepted that gastrointestinal tumors are poorly immunogenic and modern immunotherapy would not work in gastrointestinal cancers. The breakthrough has become the recognition of the mismatch repair system (MMR) that affects the microsatellite instability (MSI) and its role in the development of colorectal carcinoma (CRC). Metastatic colorectal carcinoma (mCRC) with defect MMR (dMMR) and MSI-H, resp. is immunogenic and can be a target of modern imunotherapy directed on the PD1/PD-L1 axis. Such a treatment can improve prognosis and life quality od patients with mCRC MSI-H. Immunotherapy effectiveness was shown also in a subgroup of patients with a BRAF mutation where the effectiveness of existing systemic treatment is low. The proven predictive factor is dMMR/MSI-H. PD-1 expression does not have this significance. Results of clinical studies with nivolumab and pembrolizumab result in the inclusion of these drugs in mCRC treatment algorithms. Phase II study shows nivolumab effectiveness also in pretreated metastatic anal cancer. PURPOSE: An overview of basic information on the possibilities of immunotherapy in CRC and anal cancers.Key words: cancer immunotherapy - checkpoint inhibitors - colorectal cancer - anal cancer - nivolumab - pembrolizumab Supported by MH CZ - DRO (MMCI, 00209805) I declare that, in connection with the abovementioned contribution, which I am an author, I have a conflict of interest with the following companies: BMS, Roche, Merck, Amgem and Bayer. The author declares he has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 7. 9. 2017Accepted: 5. 11. 2017.

Compact pairwise models for epidemics with multiple infectious stages on degree heterogeneous and clustered networks.

This paper presents a compact pairwise model describing the spread of multi-stage epidemics on networks. The multi-stage model corresponds to a gamma-distributed infectious period which interpolates between the classical Markovian models with exponentially distributed infectious period and epidemics with a constant infectious period. We show how the compact approach leads to a system of equations whose size is independent of the range of node degrees, thus significantly reducing the complexity of the model. Network clustering is incorporated into the model to provide a more accurate representation of realistic contact networks, and the accuracy of proposed closures is analysed for different levels of clustering and number of infection stages. Our results support recent findings that standard closure techniques are likely to perform better when the infectious period is constant.

Influence of risk-taking health behaviours of adolescents on cervical cancer prevention: a Hungarian survey.

An anonymous questionnaire survey was conducted among the Hungarian adolescents to establish their use of tobacco, alcohol and drugs in relation to sexual behaviours, knowledge of human papillomavirus (HPV) and cervical cancer, and beliefs and attitudes towards screening and vaccination. Results indicated that adolescent risk-taking health behaviours correlate with risky sexual behaviours. As risk-taking behaviours do not correlate with a better awareness of the risk associated with HPV infection, it is of crucial importance that HPV/cervical cancer preventing educational programmes shall be sensitive to this 'vulnerable' population and draw the attention of these adolescents to their increased risk of sexually transmitted diseases and undesired pregnancies. Well-designed behavioural change interventions may be effective when in addition to providing adolescents (both men and women) with clear information about the implications of an HPV infection, they also aim to improve safer sex behaviours: consistent condom usage, limiting the number of sex partners, as well as encouraging regular participation in gynaecological screenings and uptake of the HPV vaccine. As this study population demonstrated positive attitudes towards the primary and secondary prevention of cervical cancer, the free HPV vaccination for the 12-13-year-old girls in Autumn 2014 will hopefully increase the currently low uptake of the vaccine in Hungary.

Dynamics of Multi-stage Infections on Networks.

This paper investigates the dynamics of infectious diseases with a non-exponentially distributed infectious period. This is achieved by considering a multi-stage infection model on networks. Using pairwise approximation with a standard closure, a number of important characteristics of disease dynamics are derived analytically, including the final size of an epidemic and a threshold for epidemic outbreaks, and it is shown how these quantities depend on disease characteristics, as well as the number of disease stages. Stochastic simulations of dynamics on networks are performed and compared to output of pairwise models for several realistic examples of infectious diseases to illustrate the role played by the number of stages in the disease dynamics. These results show that a higher number of disease stages results in faster epidemic outbreaks with a higher peak prevalence and a larger final size of the epidemic. The agreement between the pairwise and simulation models is excellent in the cases we consider.

Exact Equations for SIR Epidemics on Tree Graphs.

We consider Markovian susceptible-infectious-removed (SIR) dynamics on time-invariant weighted contact networks where the infection and removal processes are Poisson and where network links may be directed or undirected. We prove that a particular pair-based moment closure representation generates the expected infectious time series for networks with no cycles in the underlying graph. Moreover, this "deterministic" representation of the expected behaviour of a complex heterogeneous and finite Markovian system is straightforward to evaluate numerically.

Human papillomavirus infections among Hungarian female sex workers.

The purpose of this study was to assess the human papillomavirus (HPV) prevalence in cervical, oropharyngeal and anal samples of the high-risk population of Hungarian female sex workers (FSWs). HPV testing of swab specimens from FSWs (n = 34) using polymerase chain reaction (PCR) methodology was performed. Results were compared with control group (n = 52) matched for age. Questionnaires were used to obtain data regarding participants' sexual behaviour. Data were analysed using SPSS. HPV DNA was detected in at least one location in a great majority of FSWs (82.4%), compared with 46.2% of the general female population (P < 0.05). Both the cervical and the anal samples of sex workers showed higher infection rates than those of controls (64.7% vs. 34.6% and 50.0% vs. 15.4%, respectively, P < 0.05). High-risk HPV prevalence was also significantly higher in sex workers (55.9% vs. 25.0%, P < 0.05). A significantly higher proportion of FSWs had a history of genital warts (26.5% vs. 3.8%, P < 0.05). The results suggest that condom use may not result in adequate protection from HPV infection. The high infection rates among FSWs should be viewed as a priority group for HPV and cervical cancer prevention programmes since they are sources of HPV infection for the general population.

Barriers and supportive factors in engaging cancer patients in physical activity programmes - a literature review.

BACKGROUND: Regardless of cancer type or stage of treatment, physical activity (PA) has been shown to reduce the risk of cancer recurrence and death. It is associated with a range of positive effects on patients' physical and psychological well-being, particularly in the areas of aerobic fitness, fatigue, mental health and perceived overall quality of life. However, in current oncology practice, the combination of its indication with treatment is still relatively rare. At the same time, cancer patients' participation in regular physical activity is usually very low. However, as PA is an effective method to support cancer treatment and plays an important role in prevention, it is necessary to find effective strategies to involve patients more widely in physical activities. To this end, physical activity programmes organised directly by facilities providing comprehensive cancer care appear to be very suitable. PURPOSE: This literature review maps the main barriers and facilitators to cancer patients' participation in physical activity programmes. In particular, economic factors related to health policy, reflected in the availability of this type of supportive care for patients, the level of health literacy, the organization of PA programs, health care providers - both physicians and health care workers, social support and intrapsychic influences on the part of patients play a major role. Since the implementation of physical activity programmes into the existing cancer care system is a rather challenging process, the paper also deals with the possibilities of using the Health Belief Model. In the given context, this model allows the prediction and identification of barriers and supportive factors to patients' involvement in PA programs in order to maximize their effectiveness and adapt them to the needs of patients and, at the same time, to the capabilities of a specific medical facility.

Prevalence of sexually transmitted infections in women of the Czech Republic Armed Forces: a cross-sectional pilot study.

INTRODUCTION: Sexually transmitted infections (STIs) are an everlasting health issue globally. The military environment is recognised as a high-risk setting. Human papillomavirus (HPV), Chlamydia trachomatis and Neisseria gonorrhoeae are the most frequent STIs worldwide. This prospective cross-sectional pilot study focuses on the prevalence of selected STIs in the female population of the Czech Republic's Armed Forces. METHODS: C. trachomatis, N. gonorrhoeae and HPV detection and genotyping were performed between August 2020 and December 2022 in 141 women. Participants were divided into three groups according to their military status-recruits (n=72), active soldiers (n=25) and control civilian group (n=44). Cervical smear tests were performed, and data on STI risk factors were obtained through a questionnaire. RESULTS: A significant difference in the HPV prevalence between recruits (64.5 %) and both active soldiers (46.4 %) and civilians (47.3 %) was found when adjusted for age (p=0.007 and p=0.01, respectively). Lower age of coitarche (median 16; p=0.005) and smaller agglomeration origin (p=0.013) were reported for military recruits. No difference was proven in other researched risk factors. Associations between HPV detection and the higher number of sexual partners (p=0.013), early coitarche (p=0.016) and single marital status (p=0.002) across the groups were observed. Not a single case of N. gonorrhoeae was detected in any of the 141 participants. The prevalence of C. trachomatis did not differ significantly between the three evaluated groups-recruits, control civilian group, and active soldiers (5.6%, 2.3%, 0%, respectively; p=0.567). CONCLUSIONS: This pilot study showed a significantly higher HPV prevalence in female military recruits compared with both active military and civilian women. Recruits reported earlier coitarche which is a strong STI risk factor. Further study is needed to expand on the findings of this pilot study and generate data to support adjustment of STI preventive measures within the Czech Republic Armed Forces.

Clinical impact of PAI 1 4G/5G gene polymorphism in colorectal carcinoma patients.

Plasminogen activator ihnibitor (PAI 1) belongs to the plasminogen activator system, which is part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumors. Its plasma level is normally low but 4G/4G homozygotes have higher concentrations of PAI 1. This genotype may be associated with worse prognosis and proximal location of colorectal cancer than 5G/5G homozygotes. In our prospective evaluation we examined plasma level PAI 1 (using photometric microplate method ELISA) pre-surgery and, subsequently, 6-8 weeks later, from 80 patients. For the PAI 1 rs1799889 -675 4G/5G polymorphism test the PCR amplification was used.Analysis of collected data was confirmed that significantly higher plasma levels of PAI 1 were found in patients before starting therapy, which decreased (p=0.004) after initiation of treatment. Patients with higher plasma level PAI 1 before (p=0.013) and after therapy (p=0.004) had significantly shorter survival. We found no relationship between polymorphisms of PAI 1 (-675 4G/5G) in relation to stage, survival or tumor location. PAI 1 is useful as a negative marker of prognosis and could be advantageous when planning adjuvant treatment of patients with colorectal carcinoma. Although opinions on the importance of polymorphisms of PAI 1 in relation to the prognosis are not uniform, it does seem that their role in the prognosis of patients with colorectal cancer is not essential.

[The current approach to the treatment of the patients with metastatic colorectal cancer]. / Soucasný prístup k lécbe pacientu s metastatickým kolorektálním karcinomem.

Colorectal cancer is one of the most common malignant tumors. Despite the constant promotion of prevention remains around 20- 30% of cases dia-gnosed in the metastatic stage and approximately 50- 60% of patients developed the late dissemination. In 80- 90% of them we can find already unresectable metastases. Although surgical treatment is basic modality of therapy, with using mo-dern targeted therapy in combination with chemotherapy we can achieve longterm complete remission in the cases of advanced tumor and we can significantly prolonged the life of patients with this disease now. About 40- 50% patients in advanced stages who underwent metastasectomy survives 5-years and 10year survival rate is up to 25%. When administered systemic treatment median overall survival in these cases reaches around 24 months.

[Malignant melanoma treated with radical chemotherapy, resemblance histology of melanoma to soft tissue sarcomas, case report]. / Maligní melanom lécený intenzivní chemoterapií, podobnost histologického obrazu maligního melanomu a nádoru mekkých tkání, kazuistika pacientky.

BACKGROUND: Malignant melanoma is considered to be highly resistant to chemotherapy, radiotherapy, hormonotherapy and standard immunotherapy (interleukin 2, interferon alpha). Radical surgery in the early stages of the disease is still the most efficient method. Since the development of immunotherapy and targeted therapy, the role of palliative chemotherapy for advanced disease may be changing. CASE: A case report regarding 44-year-old woman with extensive tumor of the pectoral wall with contralateral axillary lymphadenopathy is presented. On the basis of imaging methods, histology and immunohistochemistry, the tumor was defined as a sarcoma. Due to PAX7-FKHR fusion gene positivity, rhabdomyosarcoma was the most probable classification. The patient was treated with radical chemotherapy including iphosphamide, vincristine, actinomycin D and doxorubicin with the effect of partial regression of the tumor. This enabled radical surgery of the chest wall tumor. Pathology proved 70% necrosis of the tumor. A contralateral axillary dissection was performed with a finding of two lymph nodes infiltrated with melanoma. The immunohistochemistry markers S100, HMB-45 and Melan A were positive. This resulted in a reclassification of the chest wall tumor to malignant melanoma. The following PET/CT scan was negative. A massive progression of the disease occurred after 5 months. B-RAF mutation leads to a plan of targeted therapy with vemurafenib. CONCLUSION: The case demonstrates the limits of the sensitivity and specificity of immunohistochemical markers of melanoma and the ability of this tumor to imitate various tumors including soft tissue sarcomas. A rare -PAX7-FKHR fusion gene positivity considered specific for rhabdomyosarcoma was found. An extraordinary response to radical chemotherapy with surgical resection led to an improvement of the quality of life and to a prolonged survival comparable with the effect of new targeted treatment for malignant melanoma.

[Epidemiological and clinico-pathological characteristics of patients with renal carcinoma: a single institution analysis of 544 cases]. / Epidemiologická a klinicko-patologická charakteristika pacientu s renálním karcinomem: analýza 544 prípadu z jednoho centra.

BACKGROUND: The incidence of renal cell carcinoma in the Czech Republic is one of the highest in the world. Curative treatment is still possible only surgically, while in the palliative treatment, partial success was reached using targeted therapies. While prognostic factors and models are commonly used in clinical practice, unfortunately, predictive biomarkers have not been found. The aim of our study was to verify the validity of selected prognostic factors on a consecutive patient cohort from the Czech population. PATIENTS AND METHODS: The patient cohort consisted of 544 patients with RCC diagnosed and/or treated at our institute from 2003 to 2010. Individual clinical and histological prognostic factors and Heng prognostic model were validated. RESULTS: Median time of follow-up for our cohort was 42 months (range 0.3-326 months), median age at diagnosis was 62 years, and almost 64% of patients were men. Distribution of clinical stages was as follows: 46.5% of I, II. 10.7%, III. 13.1%, IV. 20%. 26.4% of patients in stage I-III relapsed. We diagnosed mainly clear cell (84.6%) and papillary carcinoma (9.2%). Initially, 95.8% of patients underwent surgical treatment, systemic adjuvant and palliative treatment was applied in 3.7 and 37.7% of patients, respectively. Palliative targeted therapy was received by a total of 163 patients (30%). In first-line targeted therapy, the following median TTP was reached (in months): 10.8 for sunitinib, 6.3 for sorafenib and 5.2 months for immunotherapy. The most significant prognostic factors (p < 0.00001) were: stage of disease (HR = 9.61), size of the primary tumor (HR = 5.83), lymph nodes (HR = 8.26), presence of sarcomatoid tumor sections in the tumor (HR = 7.29), and tumor grade (HR = 4.0). Besides these, we also confirmed the prognostic importance of presence of eosinophilic granulations in the tumor (HR = 1.91, p = 0.02). When applying the Heng prognostic model, we achieved similar results for patients treated with targeted therapies. CONCLUSION: The obtained epidemiological and clinico-pathological data are consistent with previously published data. These prognostic factors can be used for a differentiated approach to patients with RCC, both for establishing follow-up plan for patients after surgery as well as indication for targeted therapies.

New ESMO guidelines for clinical practice in metastatic colorectal cancer - commentary on changes in systemic therapy.

Commentary on the newly released European Society for Medical Oncology (ESMO) guidelines for the diagnosis and treatment of metastatic colorectal cancer (mCRC). After 6 years, individual chapters have been updated, from molecular tumor testing to diagnostic and treatment procedures to the implementation of newly registered medicinal products. The authors highlight the most important changes in the guidelines. Awareness of possible new treatments for mCRC is important to determine the treatment strategy for patients with mCRC. In this commentary, we focus primarily on the status of systemic treatment in unresectable disease.

Biomarkers as prognostic and predictive factors in patients with hepatocellular carcinoma undergoing radiological oncological interventions.

BACKGROUND: Hepatocellular carcinoma is the most common malignant liver tumor in adults and thermal ablation and transarterial embolization are important methods of therapy. Thermal ablation can be used in early stages. Methods based on the transarterial approach, especially transarterial chemoembolization, play an important role in intermediate stage diseases. The success of procedures depends not only on the biological nature and the size of the tumor, on the technical design of the procedure and on the patient's response to treatment, but also on the molecular changes associated with these procedures. In addition to classic predictive and prognostic factors including age, patient comorbidities, Child-Pugh score, tumor characteristics, presence of large surrounding vessels, and portal vein thrombosis, molecular prognostic and predictive factors (serum biomarkers) are often mentioned in studies. Currently, only a-fetoprotein is routinely used as a prognostic biomarker; however, there are studies referring to new serum biomarkers that can potentially help to classical markers and imaging methods to determine the cancer prognosis and predict the success of therapy. These biomarkers most often include g-glutamyltranspeptidase, des- g-carboxyprothrombin, some types of microRNAs, inflammatory and hypoxic substances, whose serum levels are changed by the intervention therapies. Evaluation of these molecules could lead to the optimization of the medical intervention (choice of therapy method, timing of treatment) or change the management of patient follow-up after interventions. Although several biomarkers have shown promising results, most serum biomarkers still require validation in phase III studies. PURPOSE: The aim of this work is to present a comprehensive overview of classical and molecular biomarkers that could potentially help in the prognostic stratification of patients and better predict the success and effect of radiological intervention methods.

Expression levels of transcribed ultraconserved regions uc.73 and uc.388 are altered in colorectal cancer.

OBJECTIVES: The development of colorectal cancer (CRC) is characterized by multiple genetic alterations. Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed. It has recently been proven in cancer systems that differentially expressed T-UCRs could alter the functional characteristics of malignant cells. Genome-wide profiling revealed that T-UCRs have distinct signatures in human leukemia and carcinoma. METHODS: In our study, we examined the expression levels of uc.43, uc.73, uc.134, uc.230, uc.339, uc.388 and uc.399 in 54 samples of primary colorectal carcinomas and 15 samples of non-tumoral adjacent tissues by real-time PCR. T-UCR expression levels were also correlated with commonly used clinicopathological features of CRC. RESULTS: Expression levels of uc.73 (p = 0.0139) and uc.388 (p = 0.0325) were significantly decreased in CRC tissue, and uc.73 indicated a positive correlation with overall survival (p = 0.0315). The lower expression of uc.388 was associated with the distal location of CRC (p = 0.0183), but no correlation of any evaluated T-UCR with clinical stage, grade and tumor diameter was observed. CONCLUSION: Our preliminary results suggest that uc.73 and uc.388 could be potential diagnostic and prognostic biomarkers in CRC patients.

Advancement in vaccination against Newcastle disease: recombinant HVT NDV provides high clinical protection and reduces challenge virus shedding with the absence of vaccine reactions.

Newcastle disease (ND) is a highly contagious disease of chickens causing significant economic losses worldwide. Due to the limitation in their efficacy, current vaccination strategies against ND need improvements. This study aimed to evaluate a new-generation ND vaccine for its efficacy in providing clinical protection and reducing virus shedding after challenge. Broiler chickens were vaccinated in ovo or subcutaneously at hatch with a turkey herpesvirus-based recombinant vaccine (rHVT) expressing a key protective antigen (F glycoprotein) of Newcastle disease virus (NDV). Groups of birds were challenged at 20, 27, and 40 days of age with a genotype V viscerotropic velogenic NDV strain. Protection was 57% and 81%, 100% and 95%, and 100% and 100% after the subsequent challenges in the in ovo and subcutaneously vaccinated chickens, respectively. Humoral immune response to vaccination could be detected from 3-4 wk of age. Challenge virus shedding was lower and gradually decreased over time in the vaccinated birds compared to the unvaccinated control chickens. In spite of the phylogenetic distance between the NDV F gene inserted into the vector vaccine and the challenge virus (genotype I and V, respectively), the rHVT NDV vaccine provided good clinical protection and significantly reduced challenge virus shedding.

[Significance of urokinase and its inhibitors in the invasiveness and metastasing of malignant tumors]. / Význam urokinázy a jejích inhibitoru pro invazi a metastazování zhoubných nádoru

Fibrinolysis is process, which leads to the degradation of fibrin to fibrin monomers. Fibrinolysis helps to regulate hemostasis and prevents the creation of inappropriately large thrombus, which could reduce blood flow to the bloodstream. The main enzyme involved in fibrinolysis is plasmin. Tissue plasminogen activator (tPA) and urokinase (uPA) are agents converting plasminogen into active plasmin, together with urokinase receptor (uPAR) and urokinase inhibitors (PAI 1, PAI 2, PAI 3 and protease nexin) form plasminogen activator system (PAS) which is among others also part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumours. In contrast to tPA that is fundamental in fibrinolysis, uPA plays an essential role in tissue degradation as part of physiological and pathological processes. uPAR is a GPI (glycosylphosphatidylinositol)-anchored protein. The binding of uPA to uPAR results in activation of protein tyrosine kinase, protein kinase C and MAP kinase. At the same time, direct signalling pathway via Jak/STAT cascade utilising signalling transduction of Scr-like protein tyrosine kinase have also been described. uPAR expression is regulated by many growth factors, e.g. EGF, FGF-2 and HGF. It seems that individual PAS factors are involved in the process of rendering malignant tumors invasive. To what degree this influence is essential to specific malignancies, should be answered by further research. In the article the authors present a summary of findings about the interaction of fibrinolysis and tumor process, especially on the effects of urokinase and other activators and their inhibitors in metastasis of malignant tumors. The text contains information on the factors theirs introduction into practice is still the subject of numerous discussions, but in the future, individual PAS factors could play an important role in planning treatment strategies and also could become targets of targeted therapy.

[Liver function assessment in oncology practice]. / Hodnocení jaterní funkce v onkologické praxi.

The overall condition and prognosis of a patient can be affected by impaired liver function. It applies to anticancer pharmacotherapy, liver surgery and radiological interventions. The liver condition is usually assessed by common laboratory tests and clinical examination in daily practice. Liver tests consist of aminotransferases - alanine transaminase, aspartate transaminase, bilirubin, alkaline phosphatase, gamma glutamyl transpeptidase, lactate dehydrogenase, albumin and prothrombin time, less frequently prealbumin and cholinesterase. The alkaline phosphatase and aspartate transaminase are markers of a liver damage, the alkaline phosphatase and gamma glutamyl transpeptidase are most useful as markers for cholestatic liver injury. Albumin, prealbumin, cholinesterase and prothrombin time are the markers of synthetic liver function. Bilirubin and bile acids are related to the liver transport and excretory capacity. The Child-Pugh score is used to assess prognosis of chronic liver disease, mainly cirrhosis. The examination of liver function using indocyanine green helps to determinate the extent of possible liver resection. A mathematical analysis of dynamic cholescintigraphy and a calculation of hepatic extraction fraction enables quantification of liver function. Other liver function tests are of little use in oncology.

Incidence of fatigue associated with immune checkpoint inhibitors in patients with cancer: a meta-analysis.

BACKGROUND: Fatigue is one of the most common adverse effects associated with cancer immunotherapy using checkpoint inhibitors (CPIs). Because treatment-related fatigue also frequently occurs in patients treated with non-immunological therapies, our study aimed to compare the incidence of fatigue in CPI-treated patients with that associated with non-immune therapies in randomised trials. METHODS: PubMed and ClinicalTrials.gov were searched for phase III studies using a CPI alone or in combination with chemotherapy or non-immunologic targeted therapy in the experimental arm and control arm using inactive therapies such as placebo or observation, chemotherapy, or non-immunologic targeted therapy. Adverse events listed in the full texts as well as those available from clinicaltrials.gov were reviewed for all identified studies. RESULTS: A total of 60 studies involving 41 435 patients were included in the analysis. All-grade fatigue was reported in 30.4% of patients [95% confidence interval (CI) 29.9% to 31.0%] in the immunotherapy arms of the analysed studies. Using anti-programmed cell death protein 1 agents as reference, the odds ratio (OR) for fatigue was significantly higher both for anti-cytotoxic T lymphocyte-associated antigen 4 agents (OR 1.46, 95% CI 1.04-2.04) and the combination of anti-cytotoxic T lymphocyte-associated antigen 4 and anti-programmed cell death protein agents (OR 1.43, 95% CI 1.12-1.83). Fatigue was significantly less likely to occur in patients treated with CPI compared with patients receiving chemotherapy (OR 0.79, 95% CI 0.73-0.85), but significantly was more common in patients receiving the combination of CPI/chemotherapy compared with patients receiving chemotherapy alone (OR 1.12, 95% CI 1.03-1.22). CONCLUSIONS: Although immunotherapy using CPIs was associated with treatment-related fatigue, the occurrence of all-grade fatigue was significantly higher in patients treated with chemotherapy compared with patients receiving CPIs. The risk of fatigue was higher for CPI/chemotherapy combinations than for chemotherapy alone. These results suggest that although the effects of CPIs and chemotherapy are additive, chemotherapy was the dominant cause of treatment-related fatigue in the analysed trials.