Inflammation, but not skeletal muscle index, is associated with coronavirus disease 2019 mortality in patients with cancer.

BACKGROUND & AIMS: Patients with cancer and coronavirus disease 2019 (COVID-19) have characteristics that can cause the most severe forms of the disease and higher mortality. We aimed to assess the association between computed tomography (CT)-derived muscle abnormalities, anthropometric parameters, inflammation, and mortality in patients with cancer and COVID-19. METHODS: This retrospective study included patients with cancer and COVID-19 admitted between March 1st and December 31st, 2020. All information was collected from medical records (clinical and nutritional parameters, serum albumin, and C-reactive protein [CRP]). Weight loss and body mass index (BMI) were assessed using Global Leadership Initiative on Malnutrition phenotypic criteria. Skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) at the fourth thoracic vertebra level were assessed using computed tomography scans. RESULTS: This study included 80 patients (61% men, mean age: 58 ± 17 years). Of the patients analyzed, 49% had weight loss >5%, and 14% had low BMI. The median length of hospital stay was 7 (interquartile range: 4-14 days), 27% needed mechanical ventilation, 34% died as a direct consequence of COVID-19 infection and 15% to complications associated with cancer condition. In multivariate logistic regression analysis, low SMI was associated with increased in-hospital mortality [odds ratio (OR): 4.81; 95% confidence interval (95% CI): 1.63; 14.2; p = 0.005), while CRP was associated with COVID-19-related mortality (OR: 1.08; 95% CI: 1.01; 1.15, p = 0.018). CONCLUSION: SMI independently predicts in-hospital mortality in patients with cancer and COVID-19. Additionally, an independent association was observed between CRP and mortality specifically related to COVID-19.

Strength-to-muscle radiodensity: A potential new index for muscle quality.

BACKGROUND & AIMS: Although it is widely recognized that muscle quality significantly influences adverse outcomes in patients with cancer, the precise definition of muscle quality remains elusive. The muscle quality index (MQI), also known as muscle-specific strength, is a relatively recent functional concept of muscle quality. It is obtained through the ratio of muscle strength to muscle mass, but its predictive value in patients with cancer remains unknown. In this study, we explored the prognostic significance of MQI in patients with cancer. Furthermore, we introduce and assess the prognostic potential of a novel muscle quality metric: the strength-to-muscle-radiodensity index (SMRi). METHODS: A secondary analysis was conducted on a prospective cohort study. CT scans were opportunistically used to assess body composition parameters, including skeletal muscle mass (SM in cm2) and muscle radiodensity (SMD in HU) at the third lumbar vertebra (L3). Handgrip strength (HGS) was measured. MQICT was calculated using the ratio of HGS to SM (cm2). SMRi was calculated as the ratio of HGS to SMD (HU). For analysis purposes, low MQICT and SMRi were defined using two approaches: statistical cutoffs associated with survival, and median-based distribution data. RESULTS: A total of 250 patients were included (52.8% females, 52% adults, 20-90 years). Gastrointestinal tumors and stage III-IV were the most frequent diagnosis and stages. SMRi and MQICT were strongly positively correlated (ρ = 0.71 P < 0.001). Individual components of MQICT and SMRi were also positively correlated. Patients with both low MQICT and SMRi had shorter survival (log-rank P = 0.023 and P = 0.003, respectively). When applying median distribution cutoffs, SMRi emerged as the most accurate predictor of mortality (HR adjusted 3.18, 95% CI 1.50 to 6.75, C-index: 0.71), when compared to MQICT (HR adjusted 1.49, 95% CI 0.77 to 2.87, C-index: 0.68). CONCLUSION: This study introduces the concept and potential prognostic significance of the SMRi. The physiological and clinical implications of this new index warrant further investigation across a spectrum of diseases, including cancer.

Validity of the GLIM criteria for the diagnosis of malnutrition in patients with colorectal cancer: A multicenter study on the diagnostic performance of different indicators of reduced muscle mass and disease severity.

OBJECTIVES: To assess the concurrent and predictive validity of different combinations of Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with colorectal cancer considering different indicators of reduced muscle mass (MM) and the effects of the disease. METHODS: A secondary analysis with patients with colorectal cancer. The reduced MM was assessed by arm muscle area, arm muscle circumference, calf circumference, fat-free mass index, skeletal muscle index (SMI) and skeletal muscle. Cancer diagnosis or disease staging (TNM) was considered for the etiologic criterion referred to as the effect of the disease. The other phenotypic and etiologic criteria were also evaluated, and we analyzed 13 GLIM combinations. Concurrent validity between GLIM criteria and Patient-Generated Subjective Global Assessment was evaluated. Logistic and Cox regression were used in the predictive validation. RESULTS: For concurrent validity (n = 208), most GLIM combinations (n = 6; 54.5%) presented a moderate agreement with Patient-Generated Subjective Global Assessment and none showed satisfactory sensitivity and specificity (>80%). Reduced MM evaluated by SMI and SMI were present in the GLIM combinations associated with postoperative complications (odds ratio, ≥2.0), independent of other phenotypic and etiologic criteria. The combinations with reduced MM considering any method and fixed phenotypic criteria and TNM were associated with mortality (hazard ratio, ≥2.0). CONCLUSIONS: Satisfactory concurrent validity was not verified. The GLIM diagnosis of malnutrition was associated with postoperative complications and mortality.

Predictive validity of GLIM malnutrition diagnosis in patients with colorectal cancer.

BACKGROUND: Considering that the validation of the Global Leadership Initiative on Malnutrition (GLIM) remains unclear in patients with colorectal cancer, the present study aimed to assess the agreement, accuracy, sensitivity, specificity, and prognostic effect of the GLIM on survival when compared with the Patient-Generated Subjective Global Assessment (PG-SGA). METHODS: Patients with colorectal cancer who were scheduled to undergo a routine abdominal computed tomography (CT) scan were recruited. Using the GLIM two-step approach, the patients were first screened for malnutrition by using the PG-SGA Short Form (score ≥3). The malnutrition diagnosis was based on the etiologic (disease burden [cancer] or reduced food intake) and phenotypic GLIM criteria, including weight loss, body mass index, and skeletal muscle index at the third lumbar vertebra when using the CT scans. The food intake was assessed by the PG-SGA. RESULTS: This study included 191 patients (age, 60.5 ± 11.3 years; 57% men), and 23% and 32% were malnourished according to the GLIM and the PG-SGA, respectively. The GLIM revealed fair sensitivity (64%), good agreement (kappa = 0.65), specificity (96%), and diagnostic accuracy for detecting malnutrition (area under the receiver operating characteristic curve = 0.80; 95% CI, 0.72-0.88) when compared with the PG-SGA. The malnutrition value according to the GLIM and the PG-SGA was associated with short-term survival. However, only the PG-SGA was associated with long-term survival. CONCLUSIONS: Although showing fair sensitivity, the GLIM had good agreement, specificity, and diagnostic accuracy for malnutrition detection and was an independent predictor of short-term survival in patients with colorectal cancer.

Phase angle as a marker for muscle abnormalities and function in patients with colorectal cancer.

BACKGROUND AND AIMS: Considering the applicability of phase angle (PhA) as a marker of muscle mass and function, we aimed to investigate whether PhA is a predictor of muscle abnormalities and function in patients with cancer. METHODS: In a sample of patients with colorectal cancer (CRC), PhA was obtained from measurements of resistance and reactance from bioelectrical impedance analysis. Computerized tomography imaging at the third lumbar vertebra was used to evaluate muscle abnormalities by quantifying skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD). Muscle function was assessed by handgrip strength (HGS) and gait speed (GS). RESULTS: This cross-sectional study included 190 participants (X±SD), mean age 60.5 ± 11.3 years; 57% men; 78% had cancer stages III to IV. PhA was highly correlated with SMI (r = 0.70) and moderately correlated with HGS (r = 0.54). PhA explained 48% of the SMI variability (R2 = 0.485), 21% of the SMD variability (R2 = 0.214), 26% of HGS (R2 = 0.261) and 9.8% of GS (R2 = 0.098). In the multivariate model adjusted for age, sex, body mass index, performance status, comorbidities and cancer stage, 1-degree decrease in PhA was associated with low SMI (Odds Ratio (OR) = 6.56, 95% CI: 2.90-14.86) and with low SMI and HGS combined (OR = 11.10, 95% CI: 2.61-47.25). In addition, Receiving Operating Characteristics curve analysis showed that PhA had a good diagnostic accuracy for detecting low SMI, low SMI and SMD combined, low SMD and HGS and low SMI and HGS combined (AUC = 0.81, 95% CI: 0.74-0.88; AUC = 0.88, 95% CI: 0.81-0.95; AUC = 0.80, 95% CI: 0.70-0.91; AUC = 0.82, 95% CI: 0.74-0.89; respectively). CONCLUSIONS: PhA was a predictor of muscle abnormalities and function and had a good diagnostic accuracy for detecting low muscle mass, low muscle mass and radiodensity, low muscle radiodensity and strength, and low muscle mass and strength in patients with CRC.

Frailty is associated with myosteatosis in obese patients with colorectal cancer.

BACKGROUND & AIMS: We aimed to explore the determinants of muscle fat infiltration and to investigate whether myosteatosis, assessed as muscle fat infiltration percentage (%MFI) and muscle attenuation from computed tomography (CT), is associated with frailty in a group of patients with colorectal cancer (CRC). METHODS: Cross sectional study including CRC patients. CT scan of the third lumbar vertebra was used to quantify body composition and the degree of %MFI (reported as percentage of fat within muscle area). Frailty was defined by Fried et al. (2001) as the presence of more than 3 criteria: unintentional weight loss, self-reported exhaustion, weakness (low handgrip strength), slow walking speed (gait speed) and low physical activity. Obesity was defined according to sex-and-age-specific body fat percentage (%BF) cutoff. RESULTS: A sample of 184 patients (age 60 ± 11 years; 58% men; 29% of patients with frailty) was studied. The sample was divided according to tertiles of MFI% (1st tertile 0 to 2.89%, n = 60; 2nd tertile ≥ 3.9-8.19%, n = 64; 3rd tertile ≥ 8.2-26%, n = 60). Age, females, body mass index, %BF, subcutaneous and visceral adipose tissue and the proportion of patients with frailty were significantly higher in the 3rd %MFI tertile. Phase angle and muscle attenuation were significantly lower in the 3rd %MFI tertile. The determinants of %MFI (r2 = 0.49), which was log transformed due to its normal distribution, were %BF (ß = 0.54; eß = 1.72; 95% CI: 0.032 to 0.051; P < 0.01), age (ß = 0.34; eß = 1.40; 95% CI: 0.016 to 0.032; P < 0.01) and gait speed (ß = -0.12; eß = 0.87; 95% CI: -0.84 to -0.001; P = 0.049). In addition, in obese patients (n = 74) presenting 4 or 5 frailty criteria increased the chance of having higher %MFI and lower muscle attenuation, after adjustment for sex, age and comorbidities when compared to none or 1 criteria. CONCLUSIONS: In a sample of CRC patients, %BF and gait speed were the determinants of %MFI. In addition, markers of myostetatosis were associated with frailty in the obese patients.

Comparative Analysis Between Computed Tomography and Surrogate Methods to Detect Low Muscle Mass Among Colorectal Cancer Patients.

BACKGROUND: We aimed to evaluate the agreement between computed tomography (CT) and surrogate methods applied in clinical practice for the assessment of low muscle mass. In addition, we assessed the association between different muscle-assessment methods and nutrition status, as well as the prognostic value of low muscle mass on survival in patients with colorectal cancer (CRC). METHODS: This is a cohort including 188 CRC patients with 17 months' follow-up (interquartile range: 12-23 months) for mortality. Low muscle mass was evaluated by corrected mid-upper arm muscle area (AMAc) and calf circumference, skeletal muscle mass by bioelectrical impedance analysis (BIA), muscle deficit by physical examination with the Patient-Generated Subjective Global Assessment (PG-SGA), and lumbar muscle cross-sectional area by CT (reference method). RESULTS: The prevalence of low muscle mass ranged from 9.6% to 54.3% according to the method used. The physical examination had the highest κ coefficient compared with CT. Low muscularity was associated with the presence of malnutrition, lower body fat, and low phase angle. The Cox regression models-adjusted for age, sex, and treatment 3 months before study inclusion-showed that severe muscle loss measured by BIA and CT and low muscle mass measured by PG-SGA predicted higher mortality rates. CONCLUSIONS: Compared with CT, the physical examination had the best agreement to assess low muscle mass. Low muscle mass assessed by PG-SGA, BIA, and CT showed similar prognostic values for survival.

Muscle mass assessment by computed tomography in chronic kidney disease patients: agreement with surrogate methods.

BACKGROUND/OBJECTIVES: Patients with chronic kidney disease (CKD) are subjected to muscle wasting. Therefore, it is important to investigate surrogate methods that enable the assessment of muscle mass loss in the clinical setting. We aimed to analyze the agreement between computed tomography (CT) and surrogate methods for the assessment of muscle mass in non-dialysis CKD patients. SUBJECTS/METHODS: Cross-sectional study including 233 non-dialysis patients on CKD stages 3 to 5 (61 ± 11 years; 64% men; glomerular filtration rate 22 (14-33) mL/min/1.73 m2). The muscle mass was evaluated by CT and bioelectrical impedance, skinfold thicknesses, midarm muscle circumference (MAMC), the predictive equations of Janssen and Baumgartner and the physical examination of muscle atrophy from the subjective global assessment. RESULTS: In males, the MAMC showed the best agreement with CT as indicated by the kappa test (k = 0.57, P < 0.01), sensitivity (S = 68%), specificity (S = 89%) and accuracy (area under the curve-AUC = 0.78), followed by the Baumgartner equation (kappa = 0.46, P < 0.01; sensitivity = 60%; specificity = 87% and AUC = 0.73). In female, the Baumgartner equation showed the best agreement with CT (kappa = 0.43, P < 0.01; sensitivity = 57%; specificity = 86% and AUC = 0.71). CONCLUSIONS: The MAMC and Baumgartner equation showed the best agreement with CT for the assessment of muscle mass in non-dialysis CKD patients.

Factors Associated with Sarcopenia in Patients with Colorectal Cancer.

Introduction; Sarcopenia are frequently observed in cancer patients and was associated with poor prognosis. Objectives; to determine the association of nutritional status, body composition, and clinic parameters with sarcopenia in patients with colorectal cancer (CRC). Methods; We conducted a cross-sectional study of 197 patients with CRC. The sarcopenia elements, including lumbar skeletal muscle index (SMI), handgrip strength, and gait speed were measured. The SMI was assessed by computed tomography at third lumbar vertebra. Phase angle (PA), serum albumin (SAlb), muscle attenuation (MA), and the scored patient-generated subjective global assessment (PG-SGA) were also evaluated. Univariate and multivariate analysis of factors associated with sarcopenia were performed. Results; Sarcopenia was present in 29 of 195 patients (15%) and was significantly correlated with advance age, lower body mass index (BMI), SAlb, PA, MA, higher PG-SGA score, and malnutrition (PG-SGA B). In univariate analysis, age, BMI, SAlb, PA, MA, PG-SGA score, and malnutrition (PG-SGA B) were associated with sarcopenia. Multivariable analysis revealed that BMI, SAlb, PA, MA, and PG-SGA score were independent predictors of sarcopenia. Conclusion; BMI, SAlb, PA, MA, and PG-SGA score were independent predictors of sarcopenia in patients with CRC.

Intestinal permeability measurements: general aspects and possible pitfalls.

INTRODUCTION: Disturbances of the gut barrier function have been related to a variety of diseases, including intestinal and extra-intestinal diseases. The intestinal permeability tests are considered useful tools for evaluating disease severity and to follow-up patients after a therapeutic intervention and indirectly assess barrier function. OBJECTIVE: The aims of this review were to highlight the possible factors underlying higher intestinal permeability and the clinical conditions that have been associated with this in different age range; and also provide some insight into methodological aspects. RESULTS AND DISCUSSION: Abnormal regulation of tight junction function is the main cause of altered intestinal barrier. The impaired barrier function results in higher permeation rates of administered probes through the intestinal mucosa. Lactulose and mannitol are one of the most commonly used probes. The innocuousness and easiness of intestinal permeability tests can be explored to expand the knowledge about the clinical situations in which intestinal barrier dysfunction can be an important feature. Many factors may influence the results of the test. Researchers and healthcare professionals should try to circumvent the possible pitfalls of the intestinal permeability tests to produce consistent evidences. The use of others markers of intestinal physiology may also contribute to understand the role of barrier function in different diseases.

Introducción: Alteraciones funcionales de la barrera intestinal se han relacionado con una variedad de enfermedades intestinales y también con enfermedades no intestinales. Las pruebas de permeabilidad intestinal son consideradas herramientas útiles para evaluar la gravedad de la enfermedad para el posterior seguimiento de los pacientes después de una intervención terapéutica. Objetivo: El objeto de esta revisión ha sido destacar los posibles factores que pueden estar asociados a una mayor permeabilidad intestinal y revisar condiciones clínicas que han sido asociadas en individuos de diferentes edades. También revisar ciertos aspectos metodológicos de las pruebas de permeabilidad intestinal. Resultados y discusión: Las uniones estrechas entre los enterocitos son las principales estructuras encargadas de la regulación de la barrera intestinal. Una alteración de éstas, resulta en una deficiencia en la permeabilidad intestinal y una mayor penetración de las sustancias marcadoras de permeabilidad intestinal. La lactulosa y el manitol son las sustancias marcadoras más utilizadas. La inocuidad y facilidad de los test de permeabilidad han sido de ayuda para explorar y ampliar el conocimiento de muchas condiciones clínicas en las que la disfunción de la barrera intestinal ha sido un sello distintivo. Muchos factores pueden influir en los resultados de los test de permeabilidad. Sin embargo, los investigadores y los clínicos han de tratar de eludir los posibles inconvenientes de las pruebas de permeabilidad intestinal para poder producir evidencias más consistentes. El uso de otras sustancias marcadoras de la fisiología intestinal también puede contribuir a comprender mejor el papel de la barrera intestinal en diferentes enfermedades.

Intestinal permeability and nutritional status in developmental disorders.

CONTEXT: Autism is a developmental disorder with a possible connection between dietary components and triggering or worsening of symptoms. An altered intestinal permeability might allow absorption of incompletely digested peptides (gluten and casein) that could produce opioid-like activity on the brain, causing significant changes in behavior. OBJECTIVE: To assess the intestinal permeability and nutritional status of participants with developmental disorders to determine if changes in the intestinal mucosal barrier and/or injury to the intercellular junctions have occurred that might justify application of further dietary modifications. DESIGN: To assess intestinal permeability, the research team analyzed participants urine under fasting conditions, using gas chromatography to determine chromatographic peaks. To assess nutritional status, the team determined participants heights and weights and performed a bioelectric bioimpedance examination at least 4 hours after their most recent meal. In addition, the team determined food intake using three diet diaries. They asked participants and caregivers to register each food consumed during 2 nonconsecutive weekdays and 1 weekend day. SETTING: The study occurred at the Ribeirao Preto School of Medicine, Sao Paulo University. PARTICIPANTS: Seven participants aged 9 to 23 years with developmental disorders (the developmental group, DG) completed the study. The research team recruited them through the Association of Friends of the Autistic Persons of Ribeirao Preto in Ribeirao Preto, Brazil. The control group (CG) consisted of nonsmoking healthy volunteers in the general population who were similar in age to the experimental group and did not suffer from diseases that potentially could influence nutritional status and intestinal function. INTERVENTION: To assess intestinal permeability, participants ingested 150 mL of an isosmolar solution of the sugars mannitol (2 g) and lactulose (7.5 g) under fasting conditions and the researchers collected all voided urine over a period of 5 hours. OUTCOME MEASURES: Using chromatographic peaks, the research team quantified the mannitol and lactulose in participants urine by calculating the percentage excreted in relation to the ingested amounts of sugar. This calculation gave them the lactulose-to-mannitol ratio (L/M). To evaluate nutritional status, they used data regarding bioimpedance resistance, heights, and weights to estimate lean mass and body water (in liters). They classified adults and adolescents using the body mass index (BMI). For children (2-10 y), they classified participants height-to-age and weight-to-height ratios. The research team used food intake to examine the macronutrient interval, the mean added sugar consumption, and the quantity of protein, in g/kg weight. RESULTS: Participants with developmental disorders (n = 7) were more likely to be overweight. Their usual diet revealed a high intake of lipids (%) and proteins (g/kg) (compared to reference values) and a high intake of calories (kcal) and carbohydrates (%) (compared to CG) as well as a high intake of food sources that are important contributors of casein and gluten. The DGs (n = 7) mean mannitol excretion was lower, and their L/M higher than the CGs (n = 7) (P < .05). Their increased L/M may indicate atrophy of the intestinal-mucosa surface and/or injury to the intercellular junctions or the effect of some other abnormality. The small number of participants, however, prevented more complex statistical analysis. CONCLUSIONS: Researchers need to complete additional studies to confirm the existence of abnormalities in autistic individuals intestines and to justify the use of dietary restrictions on gluten and casein to improve the symptoms of autism.