Potentially fatal complications of new systemic anticancer therapies: pearls and pitfalls in their initial management.

BACKGROUND: Various types of immunotherapy (i.e. immune checkpoint inhibitors [ICIs], chimeric antigen receptor [CAR] T-cells and bispecific T-cell engagers [BiTEs]) and antibody drug conjugates (ADCs) have been used increasingly to treat solid cancers, lymphomas and leukaemias. Patients with serious complications of these therapies can be presented to physicians of different specialties. In this narrative review we discuss potentially fatal complications of new systemic anticancer therapies and some practical considerations for their diagnosis and initial treatment. RESULTS: Clinical presentation of toxicities of new anticancer therapies may be unpredictable and nonspecific. They can mimic other more common medical conditions such as infection or stroke. If not recognized and properly treated these toxicities can progress rapidly into life-threatening conditions. ICIs can cause immune-related inflammatory disorders of various organ systems (e.g. pneumonitis or colitis), and a cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) may develop after treatment with CAR T-cells or BiTEs. The cornerstones of management of these hyper-inflammatory disorders are supportive care and systemic immunosuppressive therapy. The latter should start as soon as symptoms are mild-moderate. Similarly, some severe toxicities of ADCs also require immunosuppressive therapy. A multidisciplinary team including an oncologist/haematologist and a corresponding organ-site specialist (e.g. gastroenterologist in the case of colitis) should be involved in the diagnosis and treatment of these toxicities. CONCLUSIONS: Health professionals should be aware of potential serious complications of new systemic anticancer therapies. Early diagnosis and treatment with adequate supportive care and immunosuppressive therapy are crucial for the optimal outcome of patients with these complications.

Clinical nutrition in primary care: ESPEN position paper.

Primary care healthcare professionals (PCHPs) are pivotal in managing chronic diseases and present a unique opportunity for nutrition-related disease prevention. However, the active involvement of PCHPs in nutritional care is limited, influenced by factors like insufficient education, lack of resources, and time constraints. In this position paper The European Society for Clinical Nutrition and Metabolism (ESPEN) promotes the active engagement of PCHPs in nutritional care. We emphasize the importance of early detection of malnutrition by screening and diagnosis, particularly in all individuals presenting with risk factors such as older age, chronic disease, post-acute disease conditions and after hospitalization for any cause. ESPEN proposes a strategic roadmap to empower PCHPs in clinical nutrition, focusing on education, tools, and multidisciplinary collaboration. The aim is to integrate nutrition into medical curricula, provide simple screening tools for primary care, and establish referral pathways to address malnutrition systematically. In conclusion, we urge for collaboration with PCHP organizations to raise awareness, enhance nutrition skills, facilitate dietitian accessibility, establish multidisciplinary teams, and promote referral pathways, thereby addressing the underestimated clinical challenge of malnutrition in primary care.

Effectiveness of Nutritional Intervention Led by Clinical Dietitian in Patients at Risk of Malnutrition at the Primary Healthcare Level in Slovenia - Evaluation Study.

Introduction: Clinical dietitians play a crucial role in the nutritional support of patients at risk of malnutrition in primary care settings. The study aimed to evaluate the effect of an individualized nutritional intervention on clinically relevant outcomes for patients with chronic disease at nutritional risk. Methods: A longitudinal evaluation study was conducted in two Slovenian primary health centres. We used pre-test and post-test design. Patients with chronic disease were screened using the Malnutrition Universal Screening Tool and additional risk factors (≥70 years and BMI <22 kg/m2; lower food intake in the last five days). Patients at nutritional risk were referred to a clinical dietitian for individual nutritional intervention. The effect of the nutritional intervention was assessed six months after the patients' first visit with a clinical dietitian. Results: The sample included 94 patients. Nutritional risk was reduced significantly in high-risk and moderate-risk patients. In a subgroup of patients with a MUST score ≥1 (77 patients), body weight, BMI, Fat-Free Mass Index (FFMI), energy intake, and protein intake increased significantly (p<0.001). At the same time, the phase angle significantly increased (p<0.001), but there were no statistically significant changes in the improvement of grip strength. In a subgroup of patients with MUST score 0 (17 patients), we observed an increase in their median daily energy intake (p<0.001) and median protein intake (p=0.003). Conclusion: Nutritional intervention delivered by a clinical dietitian improved patients' nutritional intake and nutritional and functional status.

The trajectory of sarcopenia following diagnosis of prostate cancer: A systematic review and meta-analysis.

INTRODUCTION: Sarcopenia is a common skeletal muscle disorder in older people. Here we explore the prevalence of sarcopenia and its impact on men with prostate cancer. MATERIALS AND METHODS: We searched PubMed, Embase, and Web of Science databases for relevant studies with an explicit definition of sarcopenia in men with prostate cancer which were published between years 2000 and 2022. Prevalence of sarcopenia and its association with time to biochemical recurrence (BCR), progression-free survival (PFS), non-cancer mortality, overall survival (OS), and treatment-related complications in men with prostate cancer were explored. The summary prevalence, hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 24 studies comprising 3,616 patients with early and advanced prostate cancer were included. The prevalence of sarcopenia and sarcopenic obesity was 43.8% (95% CI 19.2%-68.5%) and 24.0% (95% CI 5.0%-43.1%), respectively. Sarcopenia was not associated with a shorter time to BCR (HR 0.89, 95% CI 0.64-1.23, p = 0.48), a shorter PFS (HR 1.20, 95% CI 0.73-1.97, p = 0.48), or a shorter OS (HR 1.29, 95% CI 0.90-1.85, p = 0.16). In contrast, sarcopenia was significantly associated with a higher non-cancer mortality (HR 1.85, 95% CI 1.23-2.80, p = 0.003). In four out of five studies eligible for assessment, sarcopenia was not associated with an increased risk of treatment-related complications. DISCUSSION: Sarcopenia increases the risk of death from other causes in men with prostate cancer. Patients with prostate cancer should be assessed and managed for sarcopenia in everyday clinical practice.

How Can We Advance Integrative Biology Research in Animal Science in 21st Century? Experience at University of Ljubljana from 2002 to 2022.

In this perspective analysis, we strive to answer the following question: how can we advance integrative biology research in the 21st century with lessons from animal science? At the University of Ljubljana, Biotechnical Faculty, Department of Animal Science, we share here our three lessons learned in the two decades from 2002 to 2022 that we believe could inform integrative biology, systems science, and animal science scholarship in other countries and geographies. Cultivating multiomics knowledge through a conceptual lens of integrative biology is crucial for life sciences research that can stand the test of diverse biological, clinical, and ecological contexts. Moreover, in an era of the current COVID-19 pandemic, animal nutrition and animal science, and the study of their interactions with human health (and vice versa) through integrative biology approaches hold enormous prospects and significance for systems medicine and ecosystem health.

Habits of Energy Drink Consumption among Teens in Slovenia - Focus Group Findings.

INTRODUCTION: Teachers in Slovenia have been noticing the increased consumption of energy drinks among pupils. Therefore, the purpose of this study was to investigate habits that contribute to the frequency of energy drink consumption. METHOD: 36 teens participated in the study: elementary school pupils (6th and 8th grades), general upper secondary school pupils, and secondary technical school pupils (1st and 3rd year). In the course of the study 6 group interviews were held to help investigate young people's habits and their reasons for energy drink purchase and consumption. Moreover, we investigated the influence of age on the consumption and knowledge about energy drink ingredients, as well as their influence on the body. RESULTS: Interview analysis showed that energy drink consumers are predominantly secondary school pupils. Their choice most frequently depends on the price, their taste, or the brand. What influences elementary school pupils' purchasing decisions are price, packaging, and advertisements, while secondary school pupils choose their drinks according to the lack of energy and how tired they feel. The predominant factors preventing energy drink consumption are health problems among family members and friends. Secondary school pupils know more about energy drink ingredients than elementary school pupils. CONCLUSION: On the basis of these findings, we will design a survey questionnaire for Slovenian teenagers and teachers, didactic material, and suggestions for improving educational programmes.

Risk for malnutrition in family practice non-attenders living in the community: A cross-sectional study from Slovenia.

OBJECTIVES: The aim of this study was to determine the prevalence of malnutrition and the factors associated with malnutrition in a population of family practice non-attenders. This would enable us to recognize the extent of the problem and anticipate the measures needed to improve the current situation. METHODS: This was a cross-sectional observational study in a family medicine setting. Participants were adults living in the community (≥18 y of age) who had not visited their chosen family physician in the previous 5 y (non-attenders) and who were able to participate in the study. Through the electronic system, we identified 2025 non-attenders. Data were collected by community nurses in the participants' homes. The main outcome measure was the Malnutrition Universal Screening Tool. RESULTS: The sample consisted of 1641 participants (81% response rate). Increased risk for malnutrition was determined in 216 participants (13.2%; 95% confidence interval, 11.6-14.9). The multivariate model showed a significant association of increased risk for malnutrition with age and body mass index interaction (P = 0.022); number of chronic diseases (P = 0.001); poor assessment of current health (P = 0.001); a feelings of loneliness (P <0.001); and increased pain intensity (P = 0.003). CONCLUSION: A screening program at the primary health care level could help identify patients at risk for malnutrition early. This could be followed by appropriate nutrition support, which may help to reverse or halt the malnutrition trajectory and the negative outcomes associated with poor nutritional status.

Changes in Eating Habits in Breast Cancer Patients.

INTRODUCTION: Receiving a cancer diagnosis is an important moment in anyone's life. Consequently, many patients are prepared to change their everyday habits and begin to look for advice from a wide range of sources. Women with breast cancer are particularly motivated and committed to making changes to their lifestyle and diet. The purpose of this study was to elucidate the changes in nutritional and other lifestyle habits following breast cancer diagnosis in Slovenia. A further goal was to estimate the proportion of breast cancer patients using dietary supplements and alternative diets or ascertain their desire to attend a consultation with a dietician. METHODS: A link to an online questionnaire was sent to the email addresses of members of Europa Donna and posted on their website (www.europadonna-zdruzenje.si) and Facebook page. RESULTS: A total of 102 patients were included in the study. We found that a majority of breast cancer patients changed their eating habits (68.6%) and/or physical activity level (53.9%) following diagnosis. On average, they increased their fruit and vegetable intake and reduced their intake of sugar, red meat and fat. Alternative diets were used by 29.4% of patients, with a high proportion of patients (75.5%) consuming dietary supplements. More than a half of the patients (69.6%) expressed a desire for a consultation with a dietician. CONCLUSIONS: Nutritional support during cancer treatment is part of medical treatment and has an important role to play in secondary and tertiary cancer prevention activities. More dieticians should therefore be incorporated into the health system.

Thirty-four generations of divergent selection for 8-week body weight in chickens.

Chickens of the Slovenian commercial Prelux-bro line were divergently selected over 34 generations for high and low BW at 8 wk of age. The aim of the study was to estimate responses to selection with a nonlinear model. Estimates of BW for each generation were provided by the mixed model. For fitting generation means against generation or cumulative selection differential, an exponential model was used. Estimates of realized heritability over generations were derived from regression of the response on cumulative selection differential. After 34 generations, the lines differed by approximately 2,220 g for males and 1,860 g for females. Estimates for a selection limit in the high line were 2,598.4 and 2,144.1 g, for males and females, respectively. A selection limit was not reached in the low line. Half of the selection response was obtained after approximately 6 to 8 generations in the high line and 20 to 28 generations in the low line. Estimated realized heritability decreased over generations. Heritability was larger for females than males and reduction of heritability was more rapid in the high line than in the low line. Genetic SD decreased over generations. Phenotypic SD increased over generations in the high line, but was constant in the low line in the initial 22 generations and decreased thereafter. According to the good fit of the nonlinear model and informative parameter estimates, the results confirmed the usefulness of the nonlinear model for analyzing responses to long-term selection.

Genome-wide and species-wide in silico screening for intragenic MicroRNAs in human, mouse and chicken.

MicroRNAs (miRNAs) are non-coding RNAs (ncRNAs) involved in regulation of gene expression. Intragenic miRNAs, especially those exhibiting a high degree of evolutionary conservation, have been shown to be coordinately regulated and/or expressed with their host genes, either with synergistic or antagonistic correlation patterns. However, the degree of cross-species conservation of miRNA/host gene co-location is not known and co-expression information is incomplete and fragmented among several studies. Using the genomic resources (miRBase and Ensembl) we performed a genome-wide in silico screening (GWISS) for miRNA/host gene pairs in three well-annotated vertebrate species: human, mouse, and chicken. Approximately half of currently annotated miRNA genes resided within host genes: 53.0% (849/1,600) in human, 48.8% (418/855) in mouse, and 42.0% (210/499) in chicken, which we present in a central publicly available Catalog of intragenic miRNAs (http://www.integratomics-time.com/miR-host/catalog). The miRNA genes resided within either protein-coding or ncRNA genes, which include long intergenic ncRNAs (lincRNAs) and small nucleolar RNAs (snoRNAs). Twenty-seven miRNA genes were found to be located within the same host genes in all three species and the data integration from literature and databases showed that most (26/27) have been found to be co-expressed. Particularly interesting are miRNA genes located within genes encoding for miRNA silencing machinery (DGCR8, DICER1, and SND1 in human and Cnot3, Gdcr8, Eif4e, Tnrc6b, and Xpo5 in mouse). We furthermore discuss a potential for phenotype misattribution of miRNA host gene polymorphism or gene modification studies due to possible collateral effects on miRNAs hosted within them. In conclusion, the catalog of intragenic miRNAs and identified 27 miRNA/host gene pairs with cross-species conserved co-location, co-expression, and potential co-regulation, provide excellent candidates for further functional annotation of intragenic miRNAs in health and disease.

Obesity gene atlas in mammals.

Obesity in humans has increased at an alarming rate over the past two decades and has become one of the leading public health problems worldwide. Studies have revealed a large number of genes/markers that are associated with obesity and/or obesity-related phenotypes, indicating an urgent need to develop a central database for helping the community understand the genetic complexity of obesity. In the present study, we collected a total of 1,736 obesity associated loci and created a freely available obesity database, including 1,515 protein-coding genes and 221 microRNAs (miRNAs) collected from four mammalian species: human, cattle, rat, and mouse. These loci were integrated as orthologs on comparative genomic views in human, cattle, and mouse. The database and genomic views are freely available online at: http://www.integratomics-time.com/fat_deposition. Bioinformatics analyses of the collected data revealed some potential novel obesity related molecular markers which represent focal points for testing more targeted hypotheses and designing experiments for further studies. We believe that this centralized database on obesity and adipogenesis will facilitate development of comparative systems biology approaches to address this important health issue in human and their potential applications in animals.

[Some specificities of rehabilitation of children with special needs].

INTRODUCTION: Children with special needs (with psychophysical developmental disabilities) need rehabilitation in order to live as independent life as possible. The aim of this study was to determine the amount of certain kinds of rehabilitation in children with special needs. MATERIAL AND METHODS: The study included three groups of children (total of 99 children) hospitalized at the department for extended treatment of the rehabilitation center for children. All children have mental, physical or combined disabilities, as a result of chronic disease. Treatment type and the amount (and also involvement in special schools) depended on the disability. Analysis of sex distribution showed male predominance. Most children (59 of them) were aged 0-7 (59.6%) and there were 40 children 8-17 (40.4%) years old. RESULTS: Most of the subject were involved in: occupational therapy 93 (36.8%), kinesitherapy 47 subjects (18.6%), psychomotor therapy 46 (18.2%), speach therapy 35 (13.8%), and medical therapy 32 (12.6%). School children were mostly with mental disability.

[Importance of early rehabilitation of a child with severe multiple injuries: case report]. / Znacaj rane rehablitacije tesko politraumatizovanog deteta: prikaz slucaja.

CASE PRESENTATION: This is a case presentation of an eight-year-old boy, a traffic accident victim with severe polytrauma. The boy was admitted to hospital with lacerations and contusion injuries of the left basal frontal and left temporal brain region, moderate brain tissue edema and fracture of the left clavicle which were diagnosed by CT (computer tomography). The boy was in coma (Glasgow Coma Scale--5). Oral feeding and catheter removal were established after one month. Three months later his state of consciousness improved, he could carry out simple orders, started vocalization and visited ambulance by wheel chair. Speech and independent walking were achieved 4 months after the accident. PHYSICAL THERAPY: Physical therapy included: neural-stimulation by Vojta and sclerodermal message from seventh day. Later on, speech and work therapy were applied. DRUG THERAPY: Drug therapy included: muscle relaxants and tranquilizers while orthopedic treatment meant plastic immobilization. Control CT revealed chronic subdural hemathoma in the right frontal-parietal region. The boy could walk, talk, have normal diet, and controlled sphincters four months after severe trauma. Now, he is functional and on the level of moderate mental retardation. Early rehabilitation was extremely important in his recovery.