The additional benefit of computed tomography in cancer patients: impacts of sarcopenia and cachexia on quality of life during chemotherapy.

Objective: This study evaluates the effects of sarcopenia and cachexia on the quality of life (QoL) of patients with gastrointestinal cancer during their initial cycle of chemotherapy, emphasizing the significance of computed tomography (CT) in assessing muscle mass. Materials and Methods: In this prospective study, we evaluated 60 adult patients with gastrointestinal cancer who started chemotherapy between January and December of 2017. Sarcopenia was diagnosed on the basis of CT findings, and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Results: The mean age was 60.9 years, and 33 (55.0%) of the patients were men. Of the 60 patients, 33 (55.0%) had cachexia and 14 (23.3%) had sarcopenia. Chemotherapy significantly reduced QoL, particularly in the physical, role functioning, and social domains, with no differences between the cachexia and sarcopenia groups. Conclusion: Among patients with gastrointestinal cancer submitted to chemotherapy, the chemotherapy-induced decline in QoL does not seem to differ significantly between those with cachexia or sarcopenia, as classified by CT-measured muscle mass, and those without. However, CT-based muscle mass evaluation remains crucial for guiding customized intervention strategies. Integrating this evaluation in radiological reports can provide valuable insights for planning specific care, thus improving patient QoL during treatment.

Objetivo: Este estudo avalia os efeitos da sarcopenia e da caquexia na qualidade de vida de pacientes com câncer gastrointestinal durante o ciclo inicial de quimioterapia, enfatizando a importância da tomografia computadorizada (TC) na avaliação da massa muscular. Materiais e Métodos: Estudo prospectivo com 60 pacientes adultos com câncer gastrointestinal que iniciaram quimioterapia de janeiro a dezembro de 2017. A TC foi utilizada para o diagnóstico de sarcopenia e o Quality of Life Questionnaire Core 30 da European Organization for Research and Treatment of Cancer foi utilizado para avaliar a qualidade de vida. Resultados: A média de idade dos pacientes foi 60,9 anos e 33 (55%) eram homens. Entre os pacientes, 33 (55%) eram caquéticos e 14 (24%) eram sarcopênicos. A quimioterapia reduziu significativamente a qualidade de vida, especialmente nos domínios físico, de desempenho de papéis e social, sem diferenças entre os grupos caquéticos e sarcopênicos. Conclusão: A diminuição da qualidade de vida não difere significativamente entre pacientes caquéticos/sarcopênicos e não caquéticos/não sarcopênicos com câncer gastrointestinal submetidos a quimioterapia, conforme classificado pela massa muscular medida por TC. No entanto, a avaliação da massa muscular por TC continua crucial para orientar estratégias de intervenção personalizadas. A integração dessa avaliação nos laudos radiológicos pode fornecer informações valiosas para o planejamento de cuidados específicos, melhorando a qualidade de vida dos pacientes durante o tratamento.

Mood, Anxiety, and Cognitive Alterations in Cancer Patients.

BACKGROUND AND OBJECTIVE: To analyze the cytokine profile in cerebrospinal fluid (CSF), as well as mood, anxiety, and cognition profiles in patients with CC. METHODS: One hundred and nine individuals were evaluated, 37 controls, 18 CWC, and 54 CC patients. Assessments included BDI, HADS, Digit Span, FAS-verbal, Animals/WMS-R, Matrix Reasoning and Vocabulary (WASI), and QLQ-C30. RESULTS: The CC group exhibited 62.96% depression and probable anxiety/depression, with 75.92% showing attention deficits. The CC and CWC groups demonstrated significant cognitive impairment on the WASI-Vocabulary test (CWC: 13.4 ± 2.2; CC: 15.9 ± 1.1) compared to the control group (Ct: 22.8 ± 1.6; p = 0.0002). In the QLQ-C30 scores, the CC group reported a greater perceived loss of quality of life and health deterioration (score of 17.5 ± 2.6) and lower scores on the Functional Scale (49.8 ± 4.5). The CC group had 18.52% illiteracy, 18.52% incomplete higher education, and 22.22% complete elementary education. The CC group also had lower weight (Ct: 67.8 ± 1.4; CWC: 61.7 ± 3.1; CC: 59.6 ± 1.7; p = 0.0023) and BMI (CC: 21.5 [18.3; 24.8]; Ct: 24.9 [23; 25.8]; p = 0.0021) compared to controls. Cytokines detected in the CSF were MCP-1, VEGF, IL-8, IP-10, and MIP-1ß. Higher concentrations of MCP-1 were found in cancer patients (CSC: 571.2 ± 105.8; CC: 399.5 ± 65.9; Ct: 1477 ± 0.1; p < 0.0001), along with lower levels of MIP-1ß (CC: 4345 [3060; 7353]) and VEGF (CC: 48.3 ± 2.0; CWC: 49.8 ± 3.8; Ct: 64.8 ± 3.2; p < 0.0001). CONCLUSIONS: The level of mental impairment (mood, anxiety, and cognitive deficits) correlated with cancer-associated and cachexia-associated inflammation, weight loss, low BMI, elevated C-reactive protein (CRP), leukocytosis, lymphopenia, anemia, hypoalbuminemia, and low scores on the QLQ-C30 questionnaire (Global Health Status, Functional Scale, Symptom Scale). The CC group exhibited a higher prevalence of depression/anxiety, a stronger correlation between depression and inflammation, and greater cognitive impairment in attention, reasoning, and language, alongside lower average educational attainment. The low concentration of certain cytokines in the CSF combined with elevated systemic CRP in cancer and cachexia, associated with mental disorders, presents a paradox that requires further investigation. Higher concentrations of the cytokine MCP-1 in cancer patient groups indicated a positive correlation with the preservation of language abilities in these patients.

Development of a malnutrition model in mice: Comparative evaluation of food restriction percentage and different diets.

Malnutrition is a complicated illness that affects people worldwide and is linked to higher death rates, a heightened vulnerability to infections, and delayed cognitive development. Experimental models have been constructed to comprehend the mechanisms associated with hunger. In this regard, the current study used two different types of food aiming to validate a murine model of malnutrition based on dietary restriction. The study was conducted with fifty-six Swiss male mice (eight-week-old) divided into eight groups (n=7 each) and fed the following experimental diets (10 weeks): Standard Diet (ST) ad libitum; ST 20% dietary restriction; ST 40% dietary restriction; ST 60% dietary restriction; AIN93-M diet ad libitum; AIN93-M 20% dietary restriction; AIN93-M 40% dietary restriction; AIN93-M 60% dietary restriction. Body, biochemical, and histological parameters were measured, and the restriction effects on genes related to oxidative stress (GPX1 and GPX4) in epididymal adipose tissue were evaluated. The results obtained showed that 20%, 40%, and 60% of dietary restrictions were able to reduce body weight when compared to controls, highlighting the accentuated weight loss in animals with 60% restrictions, especially those fed with AIN-93 M, which showed physical changes such as whitish skin and dull coat, voracious eating, and hunched posture. The present animal model also showed biochemical changes with hypoalbuminemia, as well as histological epididymal adipose tissue modulation. The presence of increased oxidative stress was observed when evaluating the GPX4 gene. Given the results, 60% food restriction using the AIN93-M diet was the best protocol for inducing malnutrition.

Role of the sympathetic nervous system in cancer-associated cachexia and tumor progression in tumor-bearing BALB/c mice.

BACKGROUND: Adipose and muscle tissue wasting outlines the cachectic process during tumor progression. The sympathetic nervous system (SNS) is known to promote tumor progression and research suggests that it might also contribute to cancer-associated cachexia (CAC) energetic expenditure through fat wasting. METHODS: We sympathectomized L5178Y-R tumor-bearing male BALB/c mice by intraperitoneally administering 6-hydroxydopamine to evaluate morphometric, inflammatory, and molecular indicators of CAC and tumor progression. RESULTS: Tumor burden was associated with cachexia indicators, including a 10.5% body mass index (BMI) decrease, 40.19% interscapular, 54% inguinal, and 37.17% visceral adipose tissue loss, a 12% food intake decrease, and significant (p = 0.038 and p = 0.0037) increases in the plasmatic inflammatory cytokines IL-6 and IFN-γ respectively. Sympathectomy of tumor-bearing mice was associated with attenuated BMI and visceral adipose tissue loss, decreased interscapular Ucp-1 gene expression to basal levels, and 2.6-fold reduction in Mmp-9 relative gene expression, as compared with the unsympathectomized mice control group. CONCLUSION: The SNS contributes to CAC-associated morphometric and adipose tissue alterations and promotes tumor progression in a murine model.

Physical performance and plasma metabolic profile as potential prognostic factors in metastatic lung cancer patients.

BACKGROUND: Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells. METHODS: This prospective cohort study included 55 metastatic NSCLC patients and seven age-matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis. RESULTS: We observed a higher survival rate in NSCLC patients with high performance in the timed up-and-go (+320%; p = .007), sit-to-stand (+256%; p = .01) and six-minute walking (+323%; p = .002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p > .05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (-54.2%; p < .0001) and cell proliferation (-44.9%; p = .007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance. CONCLUSION: These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism.

Low Plasma Lipids Are Associated with Relapsing and Lethal Visceral Leishmaniasis in HIV-Infected Patients.

Visceral leishmaniasis (VL) results from protozoa Leishmania infantum and L. donovani infection. This study investigated whether host factors would explain the relapses. First, susceptibility to amphotericin B of L. infantum isolates was evaluated in vitro. Then, clinical data and the lipid profile of patients with relapsing and non-relapsing VL were assessed. Susceptibility to amphotericin B was similar between the isolates. CD4+ lymphocytes were reduced in both groups of patients in the first episode and with relapsing VL. Still, the strongest blood cell indicator associated with relapses was low total lymphocyte counts. Total plasma cholesterol, high-density lipoprotein, low-density lipoprotein, and, uniquely, triglycerides of the six individuals in the first episode and twenty-three with relapsing VL were lower in relapsing patients than those in the first episode. Deceased patients had extremely low low-density lipoprotein. After CD4+ decreases, lymphocyte CD8+ reduction is the final stage of immunological failure. The lower lipid concentrations appear to be secondary to the depletion of fat stores by inflammation-induced cachexia and fat exhaustion provoked by the co-occurrence of both diseases, which can finally lead to death.

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.

Cancer-induced morphological changes in enteric glial cells in the jejunum of Walker-256 tumor-bearing rats.

Cancer-induced cachexia is associated with systemic inflammation and gastrointestinal dysfunction. How changes to cells of the enteric nervous system contribute to gut dysfunction in tumor development and cancer cachexia is unknown. Here, we tested the hypothesis that changes to enteric glia, a type of peripheral glia that surround enteric neurons and regulate gut homeostasis, are associated with tumor development and that supplementing with the antioxidant L-glutathione is protective against the changes induced. Immunohistochemistry for neurons, enteric glial cells and immune cells was performed in whole-mount preparations and frozen histological sections of the jejunum from 20 Wistar rats, distributed in 4 groups: control, tumor of Walker-256, control administered with 1 % L-glutathione, and tumor of Walker-256 administered with 1 % L-glutathione. Morphoquantitative analyses were made using Image-Pro® Plus 4.5 and ImageJ® 1.43° software. Tumor development significantly reduced neuronal and glial cell populations in the myenteric and submucosal plexuses and enlarged glial cell body area in the submucosal plexus. In contrast, tumors increased glia in the jejunal mucosa and this effect was accompanied by B-lymphocyte recruitment. GSH-supplemented diet was not sufficient to protect against changes to neurons and glia in the submucosal plexus but was partially protective in the myenteric plexus. L-glutathione had no effect on physiological parameters of cachexia but was sufficient to preserve enteric glial cell density in the myenteric plexus. These results suggest that changes to both enteric neurons and glia likely contribute to the gastrointestinal effects of tumor development and that oxidative stress contributes to these effects in the enteric nervous system.

Prevalence of sarcopenia in patients with chronic kidney disease: a global systematic review and meta-analysis.

Sarcopenia is a risk factor for adverse clinical outcomes in chronic kidney disease (CKD) patients, including mortality. Diagnosis depends on adopted consensus definition and cutoff values; thus, prevalence rates are generally heterogeneous. We conducted a systematic review and meta-analysis to investigate the global prevalence of sarcopenia and its traits across the wide spectrum of CKD. A systematic search was conducted using databases, including MEDLINE and EMBASE, for observational studies reporting the prevalence of sarcopenia. We considered sarcopenia according to the consensus definition of the European Working Group on Sarcopenia in Older People (EWGSOP), the Asian Working Group for Sarcopenia, the Foundation for the National Institutes of Health Sarcopenia Project, and the International Working Group on Sarcopenia (IWGS). Subgroup analyses by CKD stages, consensus, and gender were performed. Pooled prevalence was obtained from random-effect models. A total of 140 studies (42 041 patients) across 25 countries were included in this systematic review and meta-analyses. Global prevalence of sarcopenia was 24.5% [95% confidence interval (CI): 20.9-28.3) and did not differ among stages (P = 0.33). Prevalence varied according to the consensus definition from 11% to 30%, with no significant difference (P = 0.42). Prevalence of severe sarcopenia was 21.0% (95% CI: 11.7-32.0), with higher rates for patients on dialysis (26.2%, 95% CI: 16.6-37.1) compared to non-dialysis (3.0%, 95% CI: 0-11.1; P < 0.01). Sarcopenic obesity was observed in 10.8% (95% CI: 3.5-21.2). Regarding sarcopenia traits, low muscle strength was found in 43.4% (95%CI: 35.0-51.9), low muscle mass in 29.1% (95% CI: 23.9-34.5), and low physical performance in 38.6 (95% CI: 30.9-46.6) for overall CKD. Prevalence was only higher in patients on dialysis (50.0%, 95% CI: 41.7-57.4) compared to non-dialysis (19.6%, 95% CI: 12.8-27.3; P < 0.01) for low muscle strength. We found a high global prevalence of sarcopenia in the wide spectrum of CKD. Low muscle strength, the primary sarcopenia trait, was found in almost half of the overall population with CKD. Patients on dialysis were more prevalent to low muscle strength and severe sarcopenia. Nephrology professionals should be aware of regularly assessing sarcopenia and its traits in patients with CKD, especially those on dialysis.

The additional benefit of computed tomography in cancer patients: impacts of sarcopenia and cachexia on quality of life during chemotherapy / O benefício adicional da tomografia computadorizada no paciente oncológico: impactos da sarcopenia e caquexia na qualidade de vida durante a quimioterapia

Abstract Objective: This study evaluates the effects of sarcopenia and cachexia on the quality of life (QoL) of patients with gastrointestinal cancer during their initial cycle of chemotherapy, emphasizing the significance of computed tomography (CT) in assessing muscle mass. Materials and Methods: In this prospective study, we evaluated 60 adult patients with gastrointestinal cancer who started chemotherapy between January and December of 2017. Sarcopenia was diagnosed on the basis of CT findings, and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Results: The mean age was 60.9 years, and 33 (55.0%) of the patients were men. Of the 60 patients, 33 (55.0%) had cachexia and 14 (23.3%) had sarcopenia. Chemotherapy significantly reduced QoL, particularly in the physical, role functioning, and social domains, with no differences between the cachexia and sarcopenia groups. Conclusion: Among patients with gastrointestinal cancer submitted to chemotherapy, the chemotherapy-induced decline in QoL does not seem to differ significantly between those with cachexia or sarcopenia, as classified by CT-measured muscle mass, and those without. However, CT-based muscle mass evaluation remains crucial for guiding customized intervention strategies. Integrating this evaluation in radiological reports can provide valuable insights for planning specific care, thus improving patient QoL during treatment.

Resumo Objetivo: Este estudo avalia os efeitos da sarcopenia e da caquexia na qualidade de vida de pacientes com câncer gastrointestinal durante o ciclo inicial de quimioterapia, enfatizando a importância da tomografia computadorizada (TC) na avaliação da massa muscular. Materiais e Métodos: Estudo prospectivo com 60 pacientes adultos com câncer gastrointestinal que iniciaram quimioterapia de janeiro a dezembro de 2017. A TC foi utilizada para o diagnóstico de sarcopenia e o Quality of Life Questionnaire Core 30 da European Organization for Research and Treatment of Cancer foi utilizado para avaliar a qualidade de vida. Resultados: A média de idade dos pacientes foi 60,9 anos e 33 (55%) eram homens. Entre os pacientes, 33 (55%) eram caquéticos e 14 (24%) eram sarcopênicos. A quimioterapia reduziu significativamente a qualidade de vida, especialmente nos domínios físico, de desempenho de papéis e social, sem diferenças entre os grupos caquéticos e sarcopênicos. Conclusão: A diminuição da qualidade de vida não difere significativamente entre pacientes caquéticos/sarcopênicos e não caquéticos/não sarcopênicos com câncer gastrointestinal submetidos a quimioterapia, conforme classificado pela massa muscular medida por TC. No entanto, a avaliação da massa muscular por TC continua crucial para orientar estratégias de intervenção personalizadas. A integração dessa avaliação nos laudos radiológicos pode fornecer informações valiosas para o planejamento de cuidados específicos, melhorando a qualidade de vida dos pacientes durante o tratamento.

Peripheral insulin resistance is early, progressive, and correlated with cachexia in Walker-256 tumor-bearing rats.

Insulin (INS) resistance is often found in cancer-bearing, but its correlation with cachexia development is not completely established. This study investigated the temporal sequence of the development of INS resistance and cachexia to establish the relationship between these factors in Walker-256 tumor-bearing rats (TB rats). INS hepatic sensitivity and INS resistance-inducing factors, such as free fatty acids (FFA) and tumor necrosis factor-α (TNF-α), were also evaluated. Studies were carried out on Days 2, 5, 8, and/or 12 after inoculation of tumor cells in rats. The peripheral INS sensitivity was assessed by the INS tolerance test and the INS hepatic sensitivity in in situ liver perfusion. TB rats with 5, 8, and 12 days of tumor, but not 2 days, showed decreased peripheral INS sensitivity (INS resistance), retroperitoneal fat, and body weight, compared to healthy rats, which were more pronounced on Day 12. Gastrocnemius muscle wasting was observed only on Day 12 of tumor. The peripheral INS resistance was significantly correlated (r = -.81) with weight loss. Liver INS sensitivity of TB rats with 2 and 5 days of tumor was unchanged, compared to healthy rats. TB rats with 12 days of tumor showed increased plasma FFA and increased TNF-α in retroperitoneal fat and liver, but not in the gastrocnemius, compared to healthy rats. In conclusion, peripheral INS resistance is early, starts along with fat and weight loss and before muscle wasting, progressive, and correlated with cachexia, suggesting that it may play an important role in the pathogenesis of the cachectic process in TB rats. Therefore, early correction of INS resistance may be a therapeutic approach to prevent and treat cancer cachexia.

Pathological beige remodeling induced by cancer cachexia depends on the disease severity and involves mainly the trans-differentiation of mature white adipocytes.

In cancer associated cachexia (CAC), white adipose tissue undergoes morphofunctional and inflammatory changes that lead to tissue dysfunction and remodeling. In addition to metabolic changes in white adipose tissues (WAT), adipose tissue atrophy has been implicated in several clinical complications and poor prognoses associated with cachexia. Adipocyte atrophy may be associated with increased beige remodeling in human CAC as evidenced by the "beige remodeling" observed in preclinical models of CAC. Even though beige remodeling is associated with CAC-induced WAT dysfunction, there are still some open questions regarding their cellular origins. In this study, we investigated the development of beige remodeling in CAC from a broader perspective. In addition, we used a grading system to identify the scAT as being affected by mice weight loss early and intensely. Using different in vitro and ex-vivo techniques, we demonstrated that Lewis LLC1 cells can induce a switch from white to beige adipocytes, which is specific to this type of tumor cell. During the more advanced stages of CAC, beige adipocytes are mainly formed from the transdifferentiation of cells. According to our results, humanizing the CAC classification system is an efficient approach to defining the onset of the syndrome in a more homogeneous manner. Pathological beige remodeling occurred early in the disease course and exhibited phenotypic characteristics specific to LLC cells' secretomes. Developing therapeutic strategies that recruit beige adipocytes in vivo may be better guided by an understanding of the cellular origins of beige adipocytes emitted by CAC.

Obstrucción intestinal por Strongyloides Stercolaris: A propósito de un caso / Intestinal obstruction due to strongyloides stercolaris: About a case

RESUMEN La estrongiloidiasis comúnmente produce problemas gastrointestinales. Presentamos el caso de un varón, cadete en la marina de guerra del Perú, de 30 años, procedente de lima; que desarrolló síndrome de hiperinfección por Strongyloides Stercoralis, teniendo como antecedente el diagnóstico presuntivo de polimiositis, por lo cual recibió un ciclo corto de corticoesteroides. No portador del virus htlv 1/2. Presentó al ingreso hiporexia, debilidad generalizada, caquexia, diarrea intermitente autolimitada, intolerancia oral y leve distensión abdominal. El paciente llegó a la etapa de diseminación, lo que resultó en un daño severo a nivel intestinal. La baja excreción de larvas en las heces dificultó el diagnóstico. Se brindó tratamiento con ivermectina parenteral a dosis de 1.2ml vía subcutánea cada 48 horas por tres dosis, con buena respuesta clínica y posteriormente con buena tolerancia oral. La importancia de presentar el caso es comentar sobre el abordaje diagnóstico y terapéutico de esta geohelmintiasis endémica del Perú.

Abstract Strongyloidiasis commonly causes gastrointestinal problems. We present the case of a male, a 30-year-old cadet in the peruvian navy from lima, who developed a hyperinfection syndrome due to strongyloides stercoralis, having a presumptive diagnosis of polymyositis for which he received a short cycle of corticosteroids. He was not a carrier of the htlv 1/2 virus. Upon admission, he presented with hyporexia, generalized weakness, cachexia, intermittent self-limited diarrhea, oral intolerance, and mild abdominal distension. The patient reached the dissemination stage, resulting in severe intestinal damage. The low excretion of larvae in the feces made the diagnosis difficult. Treatment was provided with parenteral ivermectin at a dose of 1.2ml subcutaneously every 48 hours for three doses, with a good clinical response and subsequently good oral tolerance. The importance of presenting the case is to comment on the diagnostic and therapeutic approach to this endemic geohelminthiasis of peru.

Mirtazapine versus Megestrol in the Treatment of Anorexia-Cachexia Syndrome in Patients with Advanced Cancer: A Randomized, Double-Blind, Controlled Phase II Clinical Trial.

This study compared mirtazapine with megestrol in the management of cancer-related anorexia-cachexia syndrome in patients with advanced cancer. A randomized, double-blind, controlled clinical trial involving patients with advanced cancer and anorexia-cachexia syndrome was performed. Participants received mirtazapine 30 mg/day or megestrol 320 mg/day for eight weeks. The primary endpoint was the effect of mirtazapine on weight gain and the secondary endpoints were its effect on appetite, muscle strength, physical performance, body composition, adverse events, and medication adherence. Linear regression model with mixed effects was applied and a significance level of 5% was adopted. Fifty-two patients were randomized. Mean age was 65.8 ± 8.4 years. There was weight gain in 52% of the participants in the megestrol group and in 38% in the mirtazapine group after four weeks (p = 0.040). Appetite improved in 92% of the participants in the megestrol group and in 56% in the mirtazapine group after eight weeks (p = 0.007). In the sub-analysis by sex, women showed improvement in appetite (p < 0.001) and weight gain (p < 0.005) in the mirtazapine group, which was not observed in men. Mirtazapine appears to be inferior to megestrol in weight and appetite improvement. However, there may be a difference in the therapeutic response between sexes.

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.

Urinary metabolomic biomarker candidates for skeletal muscle wasting in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that affects the joints, leading to chronic synovial inflammation and local tissue destruction. Extra-articular manifestations may also occur, such as changes in body composition. Skeletal muscle wasting is often observed in patients with RA, but methods for assessing loss of muscle mass are expensive and not widely available. Metabolomic analysis has shown great potential for identifying changes in the metabolite profile of patients with autoimmune diseases. In this setting, urine metabolomic profiling in patients with RA may be a useful tool to identify skeletal muscle wasting. METHODS: Patients aged 40-70 years with RA have been recruited according to the 2010 ACR/EULAR classification criteria. Further, the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) determined the disease activity. The muscle mass was measured by Dual X-ray absorptiometry (DXA) to generate the appendicular lean mass index (ALMI) by summing the lean mass measurements for both arms and legs and dividing them by height squared (kg/height2 ). Finally, urine metabolomic analysis by 1 H nuclear magnetic resonance (1 H-NMR) spectroscopy was performed and the metabolomics data set analysed using the BAYESIL and MetaboAnalyst software packages. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied to the 1 H-NMR data, followed by Spearman's correlation analysis. The combined receiver operating characteristic curve (ROC) was calculated, as well as the logistic regression analyses to establish a diagnostic model. The significance level at P < 0.05 was set for all analyses. RESULTS: The total set of subjects investigated included 90 patients with RA. Most patients were women (86.7%), with a mean age of 56.5 ± 7.3 years old and a median DAS28-CRP of 3.0 (IQR 1.0-3.0). Fifteen metabolites were identified in the urine samples with high variable importance in projection (VIP scores) by MetaboAnalyst. Of these, dimethylglycine (r = 0.205; P = 0.053), oxoisovalerate (r = -0.203; P = 0.055), and isobutyric acid (r = -0.249; P = 0.018) were significantly correlated with ALMI. Based on the low muscle mass (ALMI ≤6.0 kg/m2 for women and ≤8.1 kg/m2 for men) a diagnostic model have been established with dimethylglycine (area under the curve [AUC] = 0.65), oxoisovalerate (AUC = 0.49), and isobutyric acid (AUC = 0.83) with significant sensitivity and specificity. CONCLUSIONS: Isobutyric acid, oxoisovalerate, and dimethylglycine from urine samples were associated with low skeletal muscle mass in patients with RA. These findings suggest that this group of metabolites may be further tested as biomarkers for identification of skeletal muscle wasting.

Relationship between sarcopenia and cachexia with prognostic markers of middle-aged and older inpatients with COVID-19: a case-control study.

PURPOSE: SARS-CoV-2 infection can lead to various manifestations beyond an inflammatory response, such as anorexia, hyposmia, and other symptoms that may increase the risk of nutritional disorders. Sarcopenia and cachexia are conditions that appear to influence COVID-19 evolution. Thus, this study aimed to evaluate sarcopenia and cachexia in hospitalized patients with COVID-19, verifying their clinical impacts and relationship with prognostic markers. METHODS: This is a case-control study involving inpatients with and without a COVID-19 diagnosis. The occurrence of sarcopenia was evaluated according to European Working Group on Sarcopenia 2 criteria. Cachexia was evaluated according to (Evans et al. in Clin Nutr 27:793-799, 2008) criteria. Inflammatory markers and the 4C Mortality Score were evaluated. RESULTS: Our study included 96 individuals, divided into two groups: COVID-19 (n = 32) and control (n = 64). The mean age of the COVID-19 group was 63.3 ± 11.8 years, and the control group had a mean age of 64.3 ± 5.5 years. No significant differences in mean age were found between the groups. The prevalence of sarcopenia and cachexia in patients with COVID-19 was 21.9% and 28.1%, respectively, while in the control group, it was 29.7% and 26.6%, respectively. Sarcopenic patients with COVID-19 had a higher risk of death (4C Mortality Score) (p = 0.038). The occurrence of sarcopenia or cachexia within the COVID-19 group was not associated with inflammatory biomarkers or a higher number of COVID-19 symptoms (p > 0.05). CONCLUSION: The presence of sarcopenia among COVID-19 patients increased the risk of mortality.

Cachexia causes time-dependent activation of the inflammasome in the liver.

BACKGROUND: Cachexia is a wasting syndrome associated with systemic inflammation and metabolic disruption. Detection of the early signs of the disease may contribute to the effective attenuation of associated symptoms. Despite playing a central role in the control of metabolism and inflammation, the liver has received little attention in cachexia. We previously described relevant disruption of metabolic pathways in the organ in an animal model of cachexia, and herein, we adopt the same model to investigate temporal onset of inflammation in the liver. The aim was thus to study inflammation in rodent liver in the well-characterized cachexia model of Walker 256 carcinosarcoma and, in addition, to describe inflammatory alterations in the liver of one cachectic colon cancer patient, as compared to one control and one weight-stable cancer patient. METHODS: Colon cancer patients (one weight stable [WSC] and one cachectic [CC]) and one patient undergoing surgery for cholelithiasis (control, n = 1) were enrolled in the study, after obtainment of fully informed consent. Eight-week-old male rats were subcutaneously inoculated with a Walker 256 carcinosarcoma cell suspension (2 × 107 cells in 1.0 mL; tumour-bearing [T]; or phosphate-buffered saline-controls [C]). The liver was excised on Days 0 (n = 5), 7 (n = 5) and 14 (n = 5) after tumour cell injection. RESULTS: In rodent cachexia, we found progressively higher numbers of CD68+ myeloid cells in the liver along cancer-cachexia development. Similar findings are described for CC, whose liver showed infiltration of the same cell type, compared with both WSC and control patient organs. In advanced rodent cachexia, hepatic phosphorylated c-Jun N-terminal kinase protein content and the inflammasome pathway protein expression were increased in relation to baseline (P < 0.05). These changes were accompanied by augmented expression of the active interleukin-1ß (IL-1ß) form (P < 0.05 for both circulating and hepatic content). CONCLUSIONS: The results show that cancer cachexia is associated with an increase in the number of myeloid cells in rodent and human liver and with modulation of hepatic inflammasome pathway. The latter contributes to the aggravation of systemic inflammation, through increased release of IL-1ß.

Redox Signaling in Chronic Kidney Disease-Associated Cachexia.

Redox signaling alterations contribute to chronic kidney disease (CKD)-associated cachexia. This review aims to summarize studies about redox pathophysiology in CKD-associated cachexia and muscle wasting and to discuss potential therapeutic approaches based on antioxidant and anti-inflammatory molecules to restore redox homeostasis. Enzymatic and non-enzymatic systems of antioxidant molecules have been studied in experimental models of kidney diseases and patients with CKD. Oxidative stress is increased by several factors present in CKD, including uremic toxins, inflammation, and metabolic and hormone alterations, leading to muscle wasting. Rehabilitative nutritional and physical exercises have shown beneficial effects for CKD-associated cachexia. Anti-inflammatory molecules have also been tested in experimental models of CKD. The importance of oxidative stress has been shown by experimental studies in which antioxidant therapies ameliorated CKD and its associated complications in the 5/6 nephrectomy model. Treatment of CKD-associated cachexia is a challenge and further studies are necessary to investigate potential therapies involving antioxidant therapy.