Survey on the knowledge and practices in anorexia of aging diagnosis and management in Japan.

BACKGROUND: Anorexia of aging (AA) is a condition in older adults that includes loss of appetite and reduced food intake. There is a lack of detailed analysis of the potential influence of educational initiatives in addressing AA. This study aimed to clarify the current state of knowledge and practice regarding AA and its relationship with the availability of continuing education opportunities among Japanese healthcare professionals involved in treating older patients. METHODS: The Japan Geriatrics Society and the Japanese Association on Sarcopenia and Frailty, in collaboration with the Society on Sarcopenia, Cachexia, and Wasting Disorders, conducted an online questionnaire survey on the knowledge and practices in AA detection and management. Questions were asked in the areas of demographics, screening, definition/diagnosis, treatment, referral, and awareness, with those who 'participate' in continuing education and professional development programmes in nutrition for their patients were classified as the 'education group' and those who 'do not participate' were classified as the 'non-education group'. The results for each question were compared. RESULTS: The analysis included 870 participants (physicians, 48%; registered dietitians, 16%; rehabilitation therapists, 14%; pharmacists, 12%; nurses, 6%; and other professionals, 5%). The education group (45%) was more likely than the non-education group (55%) to use the Mini-Nutritional Assessment Short Form (MNA-SF) to screen for AA (49% vs. 27%) and less likely not to use a validated tool (33% vs. 47%). More participants used evidence-based tools and materials for AA care (38% vs. 12%), and fewer used their clinical judgement (23% vs. 35%) or were unaware of the tools and materials (9% vs. 23%). The proportion using a team of professionals experienced in AA care were 47% and 24% of the education and non-education groups, respectively. By profession, few physicians used specific validated tools and resources for AA screening and treatment. More than half of the dietitians used the MNA-SF regardless of training opportunity availability. Regarding professional availability and team use, differences in educational opportunities were particularly large among physicians. CONCLUSIONS: Participation in continuing education programmes on nutrition is associated with responsiveness to AA screening and treatment and the availability of a team of professionals, which may influence the quality of AA treatment. Nutrition education may support the confidence of healthcare professionals working with older adults in AA with complex clinical signs and encourage them to conduct evidence-based practice.

SEOM clinical guidelines for cancer anorexia-cachexia syndrome (2023).

Cancer-related anorexia-cachexia syndrome (CACS) is a debilitating condition afflicting up to 80% of advanced-stage cancer patients. Characterized by progressive weight loss, muscle wasting, and metabolic abnormalities, CACS significantly compromises patients' quality of life and treatment outcomes. This comprehensive review navigates through its intricate physiopathology, elucidating its stages and diagnostic methodologies. CACS manifests in three distinct stages: pre-cachexia, established cachexia, and refractory cachexia. Early detection is pivotal for effective intervention and is facilitated by screening tools, complemented by nutritional assessments and professional evaluations. The diagnostic process unravels the complex interplay of metabolic dysregulation and tumor-induced factors contributing to CACS. Management strategies, tailored to individual patient profiles, encompass a spectrum of nutritional interventions. These include dietary counseling, oral nutritional supplements, and, when necessary, enteral nutrition and a judicious use of parenteral nutrition. Specific recommendations for caloric intake, protein requirements, and essential nutrients address the unique challenges posed by CACS. While pharmacological agents like megestrol acetate may be considered, their use requires careful evaluation of potential risks. At its core, this review underscores the imperative for a holistic and personalized approach to managing CACS, integrating nutritional interventions and pharmacological strategies based on a nuanced understanding of patient's condition.

Gut microbiome alterations at acute myeloid leukemia diagnosis are associated with muscle weakness and anorexia.

The gut microbiota makes critical contributions to host homeostasis, and its role in the treatment of acute myeloid leukemia (AML) has attracted attention. We investigated whether the gut microbiome is affected by AML, and whether such changes are associated with hallmarks of cachexia. Biological samples and clinical data were collected from 30 antibiotic- free AML patients at diagnosis and matched volunteers (1:1) in a multicenter, cross-sectional, prospective study. The composition and functional potential of the fecal microbiota were analyzed using shotgun metagenomics. Fecal, blood, and urinary metabolomics analyses were performed. AML patients displayed muscle weakness, anorexia, signs of altered gut function, and glycemic disorders. The composition of the fecal microbiota differed between patients with AML and control subjects, with an increase in oral bacteria. Alterations in bacterial functions and fecal metabolome support an altered redox status in the gut microbiota, which may contribute to the altered redox status observed in patients with AML. Eubacterium eligens, reduced 3-fold in AML patients, was strongly correlated with muscle strength and citrulline, a marker of enterocyte mass and function. Blautia and Parabacteroides, increased in patients with AML, were correlated with anorexia. Several bacterial taxa and metabolites (e.g., Blautia, Prevotella, phenylacetate, and hippurate) previously associated with glycemic disorders were altered. Our work revealed important perturbations in the gut microbiome of AML patients at diagnosis, which are associated with muscle strength, altered redox status, and anorexia. These findings pave the way for future mechanistic work to explore the function and therapeutic potential of the bacteria identified in this study.

Consequences of Anorexia of Aging in Hospital Settings: An Updated Review.

The anorexia of aging is a widespread problem amongst older people, particularly in the hospital setting with up to 60% affected. Despite its high prevalence anorexia often goes undiagnosed in hospital, due to a lack of standardized assessment and evidence-based management, but also lack of knowledge regarding consequences. This review summarizes current evidence for anorexia of aging specific to the hospital setting, giving an overview of correlates of appetite in hospital and consequences of anorexia. It highlights an overall scarcity of research on this important clinical problem for hospitalized cohorts. The few studies point to the importance of anorexia of aging in major health burdens for older people, namely malnutrition, sarcopenia and reduced physical performance, as well as higher mortality. Further research is needed to assess temporal sequence in pathways of causality and to develop effective interventions to combat anorexia.

Anorexia of aging: An international assessment of healthcare providers' knowledge and practice gaps.

BACKGROUND: Anorexia of aging is a common geriatric syndrome that includes loss of appetite and/or reduced food intake, with associated undernutrition, unintended weight loss, sarcopenia, functional decline, loss of independence and other adverse health outcomes. Anorexia of aging can have multiple and severe consequences and is often overlooked by healthcare professionals (HCPs). Even more concerningly, clinicians commonly accept anorexia of aging as an inevitable part of 'normal' aging. The aim of this assessment was to identify current gaps in professional knowledge and practice in identifying and managing older persons with anorexia. Results may guide educational programmes to fill the gaps identified and therefore improve patient outcomes. METHODS: This international assessment was conducted using a mixed-methods approach, including focus group interviews with subject matter experts and an electronic survey of practicing HCPs. The assessment was led by the Society on Sarcopenia, Cachexia and Wasting Disorders (SCWD) and was supported by in-country collaborating organizations. RESULTS: A quantitative survey of 26 multiple-choice questions was completed by physicians, dietitians and other HCPs (n = 1545). Most HCPs (56.8%) recognize a consistent definition of anorexia of aging as a loss of appetite and/or low food intake. Cognitive changes/dementia (91%) and dysphagia (87%) are seen as the biggest risk factors. Most respondents were confident to give nutritional (62%) and physical activity (59.4%) recommendations and engaged caregivers such as family members in supporting older adults with anorexia (80.6%). Most clinicians assessed appetite at each visit (66.7%), although weight is not measured at every visit (41.5%). Apart from the Mini-Nutritional Assessment Short Form (39%), other tools to screen for appetite loss are not frequently used or no tools are used at all (29.4%). A high number of respondents (38.7%) believe that anorexia is a normal part of aging. Results show that treatment is focused on swallowing disorders (78%), dentition issues (76%) and increasing oral intake (fortified foods [75%] and oral nutritional supplements [74%]). Nevertheless, the lack of high-quality evidence is perceived as a barrier to optimal treatment (49.2%). CONCLUSIONS: Findings from this international assessment highlight the challenges in the care of older adults with or at risk for anorexia of aging. Identifying professional practice gaps between individual HCPs and team-based gaps can provide a basis for healthcare education that is addressed at root causes, targeted to specific audiences and developed to improve individual and team practices that contribute to improving patient outcomes.

What do patients and oncologists think about the evaluation and management of cancer-related anorexia-cachexia? The Quasar_SEOM study.

INTRODUCTION: Cancer patients often suffer from malnutrition and early detection and raising awareness of nutritional issues is crucial in this population. METHODS: The Spanish Oncology Society (SEOM) conducted the Quasar_SEOM study to investigate the current impact of the Anorexia-Cachexia Syndrome (ACS). The study employed questionnaires and the Delphi method to gather input from both cancer patients and oncologists on key issues related to early detection and treatment of ACS. A total of 134 patients and 34 medical oncologists were surveyed about their experiences with ACS. The Delphi methodology was used to evaluate oncologists' perspectives of ACS management, ultimately leading to a consensus on the most critical issues. RESULTS: Despite widespread acknowledgement of malnutrition in cancer as a significant issue by 94% of oncologists, the study revealed deficiencies in knowledge and protocol implementation. A mere 65% of physicians reported being trained to identify and treat these patients, with 53% failing to address ACS in a timely manner, 30% not monitoring weight, and 59% not adhering to any clinical guidelines. The lack of experience was identified as the primary hindrance to the use of orexigens in 18% of cases. Furthermore, patients reported concerns and a perception of inadequate attention to malnutrition-related issues from their physicians. CONCLUSION: The results of this study point to a gap in the care of this syndrome and a need to improve education and follow-up of cancer patients with anorexia-cachexia.

Assessment and nonpharmacological management for patients with cancer anorexia-cachexia syndrome: a best practice implementation project.

INTRODUCTION AND AIMS: Cancer anorexia-cachexia syndrome (CACS) is a common multifactorial syndrome, which affects up to 80% patients with advanced cancer. At present, evidence to support the benefit of pharmacological intervention in the management of CACS is limited. Patients would benefit from standard procedures for early assessment and identification of cancer anorexia-cachexia, and using nonpharmacological strategies to manage patients with CACS. This best practice implementation project aimed to implement an evidence-based practice in assessing and managing patients with CACS, thereby improving the compliance of clinical practice with the best evidence and the quality of life of patients with CACS. METHODS: This was an evidence-based audit and feedback project that used a three-phase approach at a public hospital in China. Phase 1 included the development of seven evidence-based audit criteria and carrying out a baseline audit on 30 patients using the JBI's Practical Application of Clinical Evidence System in the Department of Radiation Oncology of Nanfang Hospital. Phase 2 utilized the Getting Research into Practice component of the Practical Application of Clinical Evidence System to identify barriers to compliance with best practice principles and developed strategies and resources to improve compliance. Phase 3 involved conducting a follow-up audit using the same sample size and audit criteria to assess the results of interventions implemented to improve practice and identify issues that would be addressed in future audit. RESULTS: The compliance rates of audit criteria 1, 2 and 6 were 100% at both baseline and follow-up audit. After the application of evidence, the compliance rate increased from 0 to 100% for audit criterion 3, from 0 to 76.6% for audit criterion 4, from 23 to 70% for audit criterion 5, and from 0 to 40% for audit criterion 5. CONCLUSION: The best evidence for the assessment and nonpharmacological management of cancer patients with CACS can improve clinical practice, the quality of clinical nursing, and patient satisfaction. The application of electronic informatization promotes the implementation and maintenance of best practice.

Validation of the functional assessment of anorexia/cachexia therapy instrument to assess quality of life in maintenance hemodialysis patients with cachexia.

BACKGROUND: Many patients on maintenance hemodialysis (MHD) eventually suffer from cachexia. The Functional Assessment of Anorexia/Cachexia Therapy (FAACT) is a tool used to evaluate the quality of life of patients with cachexia related to various diseases, but its suitability for use in MHD patients has yet to be verified. This study aimed to explore the validation of the FAACT in MHD patients by conducting reliability and validity tests. METHODS: Qualified MHD patients were selected to complete the FAACT and Kidney Disease Quality of Life Short Form 36 (KDQOL-36) questionnaires, and their demographic data and biochemical test results were collected from electronic medical records. Next, the Cronbach's alpha coefficient, paired sample t test and ICC were used to analyze the scale consistency. Additionally, the association between the KDQOL-36 and FAACT was analyzed using Bland-Altman plots and Pearson correlation analysis. Finally, the patients were divided into groups to evaluate discriminant validity. RESULTS: A total of 299 patients were included in this study. The Cronbach's alpha coefficients of the FAACT and its anorexia-cachexia subscale (ACS) were 0.904 and 0.842, respectively, and their ICC exceeded 0.90. The correlation coefficients between the FAACT and its items ranged from 0.146 to 0.631, and the correlation coefficients between the FAACT and KDQOL-36 dimensions ranged from 0.446 to 0.617. The Bland-Altman plots between the FAACT and KDQOL-36 showed that only 3.3% of the points were outside the 95% limits of agreement. The effects of cachexia status (present or absent) on FAACT and ACS scores had effect sizes of 0.54 (P < 0.001) and 0.60 (P < 0.001), respectively. The FAACT and ACS also significantly discriminated between patients with and without inflammation (P < 0.001). CONCLUSIONS: The FAACT and ACS have acceptable reliability and validity in MHD patients and are suitable for measuring the quality of life of MHD patients with cachexia.

Poor oral health and anorexia in older rehabilitation patients.

OBJECTIVE: To investigate the association between anorexia and comprehensive oral health status in older inpatients. BACKGROUND: Anorexia in older inpatients is a major concern, but whether it is associated with oral problems is currently unclear. METHODS: This cross-sectional study included 160 participants (42.5% men) aged ≥65 years (mean age 78.6 ± 7.9) who had been admitted to a rehabilitation hospital. A score of ≤14 on the Simplified Nutritional Appetite Questionnaire for Japanese Elderly indicated anorexia. A score of ≥3 on the Oral Health Assessment Tool (OHAT) indicated poor oral health. Malnutrition was diagnosed according to the criteria set out by the Global Leadership Initiative on Malnutrition. Multivariate logistic regression was used to investigate the association between poor oral health and anorexia and, additionally, which subcategory of the OHAT (represented by a score ≥1) was associated with anorexia. RESULTS: Anorexia and poor oral health status were observed in 86 (53.8%) and 85 (53.1%), respectively. Poor oral health was associated with anorexia after adjusting for potential confounders (adjusted odds ratio [AOR] 2.7; 95% confidence interval [CI]: 1.3-5.9). Additionally, poor status of dentures (AOR 2.6; 95% CI: 1.2-5.7) and poor oral cleanliness (AOR 3.0; 95% CI: 1.4-6.4) were independently associated with anorexia. CONCLUSIONS: Poor oral health was associated with anorexia in older inpatients. Detection of poor oral health status using a comprehensive oral health assessment may be useful for anorexic patients. Early detection for poor oral health using comprehensive oral health assessments and oral care and prosthetic treatment may be useful for anorexic patients.

Cancer-associated anorexia: Validity and performance overtime of different appetite tools among patients at their first cancer diagnosis.

BACKGROUND & AIMS: Anorexia is a frequent symptom in cancer and we aimed to assess its prevalence among patients at their first cancer diagnosis by different appetite tools and the relationship between each tool with self-reports of food intake. We also tested whether cancer anorexia influences outcomes independently of reduced food intake or body weight loss (BWL) overtime and whether BWL was associated with complications during anticancer-therapy. METHODS: Functional Assessment of Anorexia/Cachexia Therapy (FAACT) score, self-assessment of appetite, Anorexia Questionnaire (AQ) and Visual Analog Scale (VAS) were administered. Percent of food intake was used as a criterion measure of anorexia. We registered BWL and anticancer-therapy complications over 3-month-follow-up. RESULTS: 438 cancer patients from 7 cancer-centers worldwide were included. The prevalence of anorexia was 39.9% by FAACT score, 40.2% by VAS, 40.6% by the self-assessment of appetite and 65.4% by AQ. Low food intake (≤50%) was reported in 28% of patients. All appetite tools correlated with food intake percent (P < 0.0001). We documented a correlation between self-assessment of appetite, FAACT score, VAS and BWL overtime (P < 0.04). The self-assessment of appetite (P = 0.0152) and the FAACT score (P = 0.043) were associated with BWL independently of anticancer therapies. Among patients with BWL, the risk to develop complications was greater with respect to those who maintained a stable or gained body weight (P = 0.03). CONCLUSIONS: In our sample of cancer patients, FAACT score and self-assessment of appetite performed well when low food intake was used as a criterion measure, and revealed an association of anorexia with BWL, which was, in turn, related to the development of anticancer-therapy complications.

Should Loss of Appetite Be Palliated in Patients with Advanced Cancer?

OPINION STATEMENT: Loss of appetite is common among patients with advanced cancer. However, it remains controversial how, when, and if to palliate this symptom. Here, we provide an update on recent as well as past literature to address the question of whether loss of appetite should be palliated in patients with advanced cancer. In our opinion-and as discussed here-we believe that this symptom should be palliated, although perhaps not always with pharmacologic interventions.

Appetite problem in cancer patients: Pathophysiology, diagnosis, and treatment.

AIM: This study aims to review the current evidence regarding appetite problem in cancer patients, mainly focusing on pathophysiology, diagnosis, and treatment. INTRODUCTION: Anorexia is the common symptom of malnutrition in cancer patients. Recently, the understanding of the pathophysiological mechanism of the appetite problem in cancer patients has been increasing that give impact to rigorous research to find the therapies for improving appetite in cancer patients. DISCUSSION: The development of anorexia in cancer patients is a complex process that involves many cytokines, receptors, chemical mediators/substances, hormones, and peptides. Growth and differentiation factor-15 (GDF-15) and toll-like receptor (TLR-4) have recently been found to be implicated in the pathogenesis of anorexia. To help diagnose the appetite problem in cancer patients, several questionnaires can be used, starting from well-known questionnaires such as Functional Assessment of Anorexia Cachexia Therapy (FAACT), Visual Analog Scale (VAS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ30). Several drugs with different mechanisms of action have been studied to help in improving appetite in cancer patients. New repurposed agents such as anamorelin, mirtazapine, thalidomide, and eicosapentaenoic acid (EPA) have shown a beneficial effect in improving appetite and quality of life in cancer patients, however more phase 3 clinical trial studies is still needed. CONCLUSION: The pathophysiology of appetite problems in cancer patients is a complex process that involves many factors. Several drugs that target those factors have been studied, however more phase 3 clinical trial studies are needed to confirm the findings from previous studies.

A randomised, double blind, placebo-controlled trial of megestrol acetate or dexamethasone in treating symptomatic anorexia in people with advanced cancer.

This multi-site, double blind, parallel arm, fixed dose, randomised placebo controlled phase III study compared megestrol acetate 480 mg/day with dexamethasone 4 mg/day for their net effects on appetite in people with cancer anorexia. Patients with advanced cancer and anorexia for ≥ 2 weeks with a score ≤ 4 (0-10 numeric rating scale (NRS) 0 = no appetite, 10 = best possible appetite) were recruited. Participants received megestrol 480 mg or dexamethasone 4 mg or placebo daily for up to 4 weeks. Primary outcomes were at day 7. Responders were defined as having a ≥ 25% improvement in NRS over baseline. There were 190 people randomised (megestrol acetate n = 61; dexamethasone n = 67, placebo n = 62). At week 1 (primary endpoint), 79·3% in the megestrol group, 65·5% in the dexamethasone group and 58·5% in the placebo group (p = 0.067) were responders. No differences in performance status or quality of life were reported. Treatment emergent adverse events were frequent (90·4% of participants), and included altered mood and insomnia. Hyperglycemia and deep vein thromboses were more frequent when on dexamethasone than the other two arms. There was no difference in groups between the three arms, with no benefit seen over placebo with anorexia improving in all arms.Trail registration: The trial was registered on 19/08/2008 with the Australian New Zealand Clinical Trials Registry (ACTRN12608000405314).

Anorexia Readiness Syndrome - about the need for early detection of dietary restrictions. Pilot study findings. / Syndrom gotowosci anorektycznej ­ o potrzebie wczesnego rozpoznania restrykcji zywieniowych. Wyniki badan pilotazowych.

OBJECTIVES: The pilot study aimed to determine the Anorexia Readiness Syndrome severity in a population of children aged 10 to 17 years according to general and sport class attendance. METHODS: The following instrumentswere used: the Anorexia Readiness Syndrome inventory (SGA-12), to identify anorexic tendencies in adolescents aged 10 to 17 years, the Eating Disorders in Youth - Questionnaire (EDY-Q) inventory by Hilbert and van Dyck (the results of work on the Polish version of the instrument - in preparation) to assess eating disorders in children, and a questionnaire to obtain the respondents' details such as the date of birth, gender, chronic diseases, height and weight. RESULTS: In the study sample, a higher ARS severity was observed among the girls compared to the boys. Higher levels of anorexia readiness were seen in physically active subjects with a lower body mass index. The SGA-12 inventory does not correlate with the EDY-Q-PL, but factor I "anorexic tendencies and statements" demonstrates important relations to the total score of the EDY-Q-PL. CONCLUSIONS: It seems that the SGA-12 inventory can help identify ARS children and adolescents (including boys) to a greater extent than the previous tool (Questionnaire for testing individual attitude towards food); it helps determine the severity of anorexic behaviours within two factors and suggests the areas of intervention aimed at psychoprevention.

Using real patients in e-learning: case-based online training in child and adolescent psychiatry.

Objectives: In undergraduate medical education and in the subject of child and adolescent psychiatry, examining young patients face-to-face is a key element of teaching. With the abrupt shutdown of face-to-face teaching caused by the SARS-CoV-2 pandemic, a case-based online training program integrating audio and video of real patients was developed. Methods: The blended learning platform CaseTrain guides medical students in their final year through real child-psychiatric patient cases, such as anorexia, autism, or attention deficit disorder, through presentation of video and audio of real patients and parents. The teaching format complements lectures on child psychiatric topics, comprising asynchronous elements (self-study using the digital material) as well as synchronous elements (web-conferences with a specialist). Learning objectives for students were set to develop knowledge of the spectra of psychiatric disorders that affect children and to recognize approaches how to assess and manage common psychiatric problems of childhood and adolescence. Results: The feedback from medical students through oral and written evaluation was positive. They appreciated getting to know 'real-world patients' in times of such a pandemic, to learn explorative techniques from role models, and to be in close contact with the supervising specialist. In consequence of critical feedback on the length of some video sequences, these training units will undergo revision. Conclusions: Case-based online training may continue to be a useful option in a post-pandemic future as integral part of medical education, complementing face-to-face lectures and training in (child) psychiatry.

Association between anorexia and hyposalivation in community-dwelling older adults in Japan: a 6-year longitudinal study.

BACKGROUND: Hyposalivation is associated with the nutritional status. Anorexia of ageing, defined as an age-related decrease in appetite and food intake, presents even in healthy adults and is considered an independent predictor of malnutrition, frailty, and mortality. However, the relationship between anorexia and hyposalivation of ageing is unclear. Thus, the present longitudinal study aimed to investigate the incidence of hyposalivation and its relationship with anorexia in community-dwelling older people in Japan. METHODS: The study population comprised 220 individuals (80 men and 140 women) aged 65-86 years at baseline. The participants underwent comprehensive health check-ups, including dental examinations and anthropometry, and face-to-face interviews in 2013 and 2019. Hyposalivation was determined on the basis of the unstimulated salivary flow rate measured using the modified cotton roll method. Anorexia was defined as a score of ≤29 in the Japanese version of the Council on Nutrition Appetite Questionnaire. Logistic regression analyses were used to test whether the presence of anorexia at baseline was an independent predictor of hyposalivation. RESULTS: Hyposalivation developed at a rate of 19.5% during the 6-year observation period. Anorexia was observed in 95 (43.2%) participants at baseline. After adjusting for potential confounding factors, anorexia (adjusted odds ratio [AOR], 2.65; 95% confidence interval [CI], 1.26-5.57) and polypharmacy (AOR, 3.29; CI, 1.06-10.19) were significant predictors of hyposalivation. CONCLUSION: Loss of appetite is independently correlated with and a risk factor for hyposalivation in older adults. Anorexia of ageing may have negative effects on the salivary flow rate in such settings. Salivation should be a standard feature in clinical assessments of the older adults.

Association of lenvatinib plasma concentration with clinical efficacy and adverse events in patients with hepatocellular carcinoma.

PURPOSE: This study aimed to examine the association between the trough plasma concentration of lenvatinib with the objective response rate (ORR) and adverse events in patients with hepatocellular carcinoma (HCC). METHODS: Twenty-one patients with HCC who received lenvatinib were enrolled. We examined the median trough concentration (Ctrough median) of plasma lenvatinib until the first clinical response evaluation. The receiver-operating characteristic curve was drawn to show the discrimination potential of the Ctrough median for the ORR, using the modified Response Evaluation Criteria in Solid Tumors. Adverse events were graded based on the Common Terminology Criteria for Adverse Events (ver. 5.0). RESULTS: The Ctrough median values in the complete response and partial response group were significantly higher than those in the stable disease and progressive disease groups. The ORR was significantly higher in the high-Ctrough median group (≥ 42.68 ng/mL) than in the low-Ctrough median group (< 42.68 ng/mL) (80.0% vs. 18.2%; p = 0.0089). Although there was no difference in the occurrence of most adverse events between the high- and low-Ctrough median groups, the occurrence of any grade anorexia (100.0% vs. 45.5%; p = 0.0124) and grade 3 serious hypertension (70.0% vs. 18.2%; p = 0.0300) was significantly higher in the high-Ctrough median group than in the low-Ctrough median group. Multivariate analysis showed that high-Ctrough median was significantly associated with ORR development (odds ratio, 15.00; 95% confidence interval, 1.63-138.16; p = 0.0168). CONCLUSION: Maintaining Ctrough median above 42.68 ng/mL was crucial for achieving the ORR in patients with HCC.

MOMENTUM: A Phase I Trial Investigating 2 Schedules of Capecitabine With Aflibercept in Patients With Gastrointestinal and Breast Cancer.

BACKGROUND: Although data from preclinical and clinical studies provide a strong rationale for combining capecitabine with anti-angiogenic agents, clinical development of this fluoropyrimidine in combination with aflibercept has lagged behind other treatments. We conducted a nonrandomized, noncomparative, 2-arm, phase I trial to address this unmet need. PATIENTS AND METHODS: Patients with chemorefractory gastrointestinal and breast cancer were sequentially recruited into a continuous (Arm A, starting dose 1100 mg/m2/day) or intermittent (Arm B, 2 weeks on/1 week off, starting dose 1700 mg/m2/day) capecitabine dosing arm. Aflibercept was administered at a flat dose of 6 mg/kg every 3 weeks in both arms. A classical 3 + 3, dose-escalation design was used. The primary objective was to establish the maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended dose for phase II trials. RESULTS: Thirty-eight eligible patients were recruited of whom 33 were assessable for DLTs (15 in arm A and 18 in arm B). Fourteen had colorectal cancer, 8 gastric cancer, and 11 breast cancer. DLTs included grade 2 hand-foot syndrome, grade 2 anorexia considered unacceptable by the patient, and grade 3 hypertension. The recommended dose for phase II trials for capecitabine was established at 1300 mg/m2/day in Arm A and 2500 mg/m2/day in Arm B with treatment-related grade ≥ 3 adverse events occurring in 47% and 50% of patients, respectively. Among 26 assessable patients, the objective response rate was 15.4% in Arm A and 7.7% in Arm B. CONCLUSION: Combining capecitabine with aflibercept is feasible and associated with a manageable safety profile and some anti-tumor activity in patients with chemorefractory gastrointestinal and breast cancer.

Computer-aided therapeutic diagnosis for anorexia.

BACKGROUND: Anorexia nervosa is a clinical disorder syndrome of the wide spectrum without a fully recognized etiology. The necessary issue in the clinical diagnostic process is to detect the causes of this disease (e.g., my body image, food, family, peers), which the therapist gradually comes to by verifying assumptions using proper methods and tools for diagnostic process. When a person is diagnosed with anorexia, a clinician (a doctor, a therapist or a psychologist) proposes a therapeutic diagnosis and considers the kind of treatment that should be applied. This process is also continued during therapeutic diagnosis. In both cases, it is recommended to apply computer-aided tools designed for testing and confirming the assumptions made by a psychologist. The paper aims to present the computer-aided therapeutic diagnosis method for anorexia. The proposed method consists of 4 stages: free statements of a patient about his/her body image, the general sentiment analysis of statement based on Recurrent Neural Network, assessment of the intensity of five basic emotions: happiness, anger, sadness, fear and disgust (using the Nencki Affective Word List and conversion of words to their basic form), and the assessment of particular areas of difficulties-the sentiment analysis based on the dictionary approach was applied. RESULTS: The sentiment analysis of a document achieved 72% and 51% of effectiveness, respectively, for RNN and dictionary-based methods. The intensity of sadness (emotion) occurring within the dictionary method is differentiated between control and research group at the level of 10%. CONCLUSION: The quick access to the sentiment analysis of a statement on the image of patient's body, emotions experienced by the patient and particular areas of difficulties of people prone to the anorexia nervosa disorders, may help to establish the diagnosis in a very short time and start an immediate therapy. The proposed automatic method helps to avoid patient's aversions towards the therapy, which may include avoiding patient-therapist communication, talking about less essential topics, coming late for the sessions. These circumstances can guarantee promising prognosis for recovering.