Future lines of research on phase angle: Strengths and limitations.

Bioelectrical impedance analysis (BIA) is the most widely used technique in body composition analysis. When we focus the use of phase sensitive BIA on its raw parameters Resistance (R), Reactance (Xc) and Phase Angle (PhA), we eliminate the bias of using predictive equations based on reference models. In particular PhA, have demonstrated their prognostic utility in multiple aspects of health and disease. In recent years, as a strong association between prognostic and diagnostic factors has been observed, scientific interest in the utility of PhA has increased. In the different fields of knowledge in biomedical research, there are different ways of assessing the impact of a scientific-technical aspect such as PhA. Single frequency with phase detection bioimpedance analysis (SF-BIA) using a 50 kHz single frequency device and tetrapolar wrist-ankle electrode placement is the most widely used bioimpedance approach for characterization of whole-body composition. However, the incorporation of vector representation of raw bioelectrical parameters and direct mathematical calculations without the need for regression equations for the analysis of body compartments has been one of the most important aspects for the development of research in this area. These results provide new evidence for the validity of phase-sensitive bioelectrical measurements as biomarkers of fluid and nutritional status. To enable the development of clinical research that provides consistent results, it is essential to establish appropriate standardization of PhA measurement techniques. Standardization of test protocols will facilitate the diagnosis and assessment of the risk associated with reduced PhA and the evaluation of changes in response to therapeutic interventions. In this paper, we describe and overview the value of PhA in biomedical research, technical and instrumental aspects of PhA research, analysis of Areas of clinical research (cancer patients, digestive and liver diseases, critical and surgical patients, Respiratory, infectious, and COVID-19, obesity and metabolic diseases, Heart and kidney failure, Malnutrition and sarcopenia), characterisation of the different research outcomes, Morphofunctional assessment in disease-related malnutrition and other metabolic disorders: validation of PhA with reference clinical practice techniques, strengths and limitations. Based on the detailed study of the measurement technique, some of the key issues to be considered in future PhA research. On the other hand, it is important to assess the clinical conditions and the phenotype of the patients, as well as to establish a disease-specific clinical profile. The appropriate selection of the most critical outcomes is another fundamental aspect of research.

Phase angle and COVID-19: A systematic review with meta-analysis.

Phase angle (PhA) has been identified as a poor prognostic factor in patients with COVID-19. This study aimed to achieve a systematic review, where we discussed the potential role of PhA value as a prognostic marker of adverse clinical outcomes such as mortality and complication in hospitalized with SARS-CoV2 infection and established the strength of recommendations for use. A systematic literature review with meta-analysis was done in the main electronic databases from 2020 to January 2023. The selected articles had to investigate adverse consequences of the COVID-19 population and raw bioimpedance parameters such as PhA and published in peer-reviewed journals. GRADE tools regarded the quality of the methodology. The review protocol was registered in PROSPERO. Only eight studies, 483 studies, were eligible for the analysis. In general, differences in PhA were seen between the comparative study groups. Patients with a low PhA experienced poor outcomes. A low PhA was associated with a significantly increased mortality risk [RR: 2.44; 95% CI (1.20-4.99), p = 0.01; I2 = 79% (p = 0.0008)] and higher complications risk [OR: 3.47, 95% CI (1.16 - 10.37), p = 0.03; I2 = 82% (p = 0.004)] in COVID-19 patients. Our analysis showed four evidence-based recommendations on the prognostic value of PhA with two strong recommendations, one of moderate and another of low-moderate quality, for predicting mortality and complications, respectively. We recommend using PhA as a prognostic marker for mortality and complications in this population. Although the results are promising, future studies must identify the PhA cut-off to guide therapeutic decisions more precisely.Registration code in PROSPERO: CRD42023391044.

Malnutrition management of hospitalized patients with diabetes/hyperglycemia and COVID-19 infection.

Diabetes mellitus and/or hyperglycemia are highly prevalent medical conditions in patients hospitalized for coronavirus disease 2019 (COVID-19) and are associated with adverse outcomes. In addition, COVID-19 itself can provoke fluctuating and high glucose levels that can be difficult to manage upon hospitalization. Hospitalized patients with COVID-19 are at high risk of malnutrition due to an increase in nutritional requirements and a severe acute inflammatory response. The management of patients with diabetes/hyperglycemia and COVID-19 is challenging and requires a specific nutritional approach, the purpose of which is to fulfill the nutritional requirements while maintaining an optimal glycemic control. In this study, an expert group of nutritional endocrinologists carried out a qualitative literature review and provided recommendations based on evidence and guidelines, when available, or on their own experience. The optimal care based on these recommendations was compared with the routine bedside care as reported by a panel of physicians (mainly, endocrinologists, geriatricians, and internists) treating patients with diabetes/hyperglycemia and COVID-19 in their daily practice. Early screening and diagnosis, a diabetes-specific therapeutic approach, and a close malnutrition monitoring are essential to improve the clinical outcomes of these patients. In conclusion, the proposed recommendations are intended to provide a useful guide on the clinical management of malnutrition in patients with COVID-19 and diabetes/hyperglycemia, in order to improve their outcomes and accelerate their recovery. The comparison of the recommended optimal care with routine clinical practice could aid to identify gaps in knowledge, implementation difficulties, and areas for improvement in the management of malnutrition in this population.

Post-Intensive Care Unit Multidisciplinary Approach in Patients with Severe Bilateral SARS-CoV-2 Pneumonia.

Background: Short and long-term sequelae after admission to the intensive care unit (ICU) for coronavirus disease 2019 (COVID-19) are to be expected, which makes multidisciplinary care key in the support of physical and cognitive recovery. Objective: To describe, from a multidisciplinary perspective, the sequelae one month after hospital discharge among patients who required ICU admission for severe COVID-19 pneumonia. Design: Prospective cohort study. Environment: Multidisciplinary outpatient clinic. Population: Patients with severe COVID-19 pneumonia, post- ICU admission. Methods: A total of 104 patients completed the study in the multidisciplinary outpatient clinic. The tests performed included spirometry, measurement of respiratory muscle pressure, loss of body cell mass (BCM) and BCM index (BCMI), general joint and muscular mobility, the short physical performance battery (SPPB or Guralnik test), grip strength with hand dynamometer, the six-minute walk test (6-MWT), the functional assessment of chronic illness therapy-fatigue scale (FACIT-F), the European quality of life-5 dimensions (EQ-5D), the Barthel index and the Montreal cognitive assessment test (MoCA). While rehabilitation was not necessary for 23 patients, 38 patients attended group rehabilitation sessions and other 43 patients received home rehabilitation. Endpoints: The main sequelae detected in patients were fatigue (75.96%), dyspnoea (64.42%) and oxygen therapy on discharge (37.5%). The MoCA showed a mean score compatible with mild cognitive decline. The main impairment of joint mobility was limited shoulder (11.54%) and shoulder girdle (2.88%) mobility; whereas for muscle mobility, lower limb limitations (16.35%) were the main dysfunction. Distal neuropathy was present in 23.08% of patients, most frequently located in lower limbs (15.38%). Finally, 50% of patients reported moderate limitation in the EQ-5D, with a mean score of 60.62 points (SD 20.15) in perceived quality of life. Conclusions: Our findings support the need for a multidisciplinary and comprehensive evaluation of patients after ICU admission for COVID-19 because of the wide range of sequelae, which also mean that these patients need a long-term follow-up. Impact on clinical rehabilitation: This study provides data supporting the key role of rehabilitation during the follow-up of severe patients, thus facilitating their reintegration in society and a suitable adaptation to daily living.

Predictors of Sarcopenia in Outpatients with Post-Critical SARS-CoV2 Disease. Nutritional Ultrasound of Rectus Femoris Muscle, a Potential Tool.

Background and Objectives: The loss of muscle mass in post-critical COVID-19 outpatients is difficult to assess due to the limitations of techniques and the high prevalence of obesity. Ultrasound is an emerging technique for evaluating body composition. The aim is to evaluate sarcopenia and its risk factors, determining ultrasound usefulness as a potential tool for this purpose according to established techniques, such as the bioimpedance vector analysis (BIVA), handgrip strength, and timed up-and-go test. Methods: This is a transversal study of 30 post-critical COVID-19 outpatients. We evaluated nutritional status by ultrasound (Rectus Femoris-cross-sectional-area (RF-CSA), thickness, and subcutaneous-adipose-tissue), BIVA, handgrip strength, timed up-and-go test, and clinical variables during admission. Results: According to The European Society for Clinical Nutrition and Metabolism and the European Association for the Study of Obesity (ESPEN&EASO) Consensus for Sarcopenic and Obesity, in terms of excess fat mass and decreased lean mass, the prevalence of class-1 sarcopenic obesity was 23.4% (n = 7), and class-2 sarcopenic obesity was 33.3% (n = 10) in our study. A total of 46.7% (n = 14) of patients had a handgrip strength below the 10th percentile, and 30% (n = 9) achieved a time greater than 10s in the timed up-and-go test. There were strong correlations between the different techniques that evaluated the morphological (BIVA, Ultrasound) and functional measurements of muscle. Intensive care unit stay, mechanical ventilation, and age all conditioned the presence of sarcopenia in COVID-19 outpatients (R2 = 0.488, p = 0.002). Predictive models for sarcopenic diagnosis based on a skeletal muscle index estimation were established by RF-CSA (R2 0.792, standard error of estimate (SEE) 1.10, p < 0.001), muscle-thickness (R2 0.774, SEE 1.14, p < 0.001), and handgrip strength (R2 0.856, SEE 0.92, p < 0.001). RF-CSA/weight of 5.3 cm2/kg × 100 was the cut-off value for predicting sarcopenia in post-critical COVID-19 outpatients, with 88.2 sensitivity and 69.2% specificity. Conclusion: More than half of the post-critical COVID-19 survivors had sarcopenic obesity and functional impairment of handgrip strength. Intensive care unit stay, age, and mechanical ventilation all predict sarcopenia. An ultrasound, when applied to the assessment of body composition in post-critical COVID-19 patients, provided the possibility of assessing sarcopenia in this population.

Overhydration Assessed Using Bioelectrical Impedance Vector Analysis Adversely Affects 90-Day Clinical Outcome among SARS-CoV2 Patients: A New Approach.

BACKGROUND: COVID-19 has taken on pandemic proportions with growing interest in prognostic factors. Overhydration is a risk factor for mortality in several medical conditions with its role in COVID-19, assessed with bioelectrical impedance (BI), gaining research interest. COVID-19 affects hydration status. The aim was to determine the hydration predictive role on 90 d survival COVID-19 and to compare BI assessments with traditional measures of hydration. METHODS: We studied 127 consecutive COVID-19 patients. Hydration status was estimated using a 50 kHz phase-sensitive BI and estimated, compared with clinical scores and laboratory markers to predict mortality. RESULTS: Non-surviving COVID-19 patients had significantly higher hydration 85.2% (76.9-89.3) vs. 73.7% (73.2-82.1) and extracellular water/total body water (ECW/TBW) 0.67 (0.59-0.75) vs. 0.54 (0.48-0.61) (p = 0.001, respectively), compared to surviving. Patients in the highest hydration tertile had increased mortality (p = 0.012), Intensive Care Unit (ICU) admission (p = 0.027), COVID-19 SEIMC score (p = 0.003), and inflammation biomarkers [CRP/prealbumin (p = 0.011)]. Multivariate analysis revealed that hydration status was associated with increased mortality. HR was 2.967 (95%CI, 1.459-6.032, p < 0.001) for hydration and 2.528 (95%CI, 1.664-3.843, p < 0.001) for ECW/TBW, which were significantly greater than traditional measures: CRP/prealbumin 3.057(95%CI, 0.906-10.308, p = 0.072) or BUN/creatinine 1.861 (95%CI, 1.375-2.520, p < 0.001). Hydration > 76.15% or ECW/TBW > 0.58 were the cut-off values predicting COVID-19 mortality with 81.3% and 93.8% sensitivity and 64 and 67.6% specificity, respectively. Hydration status offers a sensitive and specific prognostic test at admission, compared to established poor prognosis parameters. CONCLUSIONS AND RELEVANCE: Overhydration, indicated as high hydration (>76.15%) and ECW/TBW (>0.58), were significant predictors of COVID-19 mortality. These findings suggest that hydration evaluation with 50 kHz phase-sensitive BI measurements should be routinely included in the clinical assessment of COVID-19 patients at hospital admission, to identify increased mortality risk patients and assist medical care.

[Investigation in clinical nutrition and generation of new evidence: the NutriCOVer program]. / Investigación en nutrición clínica y generación de nuevas evidencias: el programa NutriCOVer.

Introduction: NutriCOVer is a global research program sponsored by Nutricia to support initiatives in clinical investigation in 16 countries worldwide. The program's objective is to adapt nutritional care to the needs of patients with COVID-19 who have been discharged from the intensive care unit. In Spain - a reference country for the NutriCOVer program - three research projects are being carried out. These studies analyze the clinical course of COVID-19 patients from a nutritional point of view, evaluating relevant aspects such as the prevalence and evolution of malnutrition and sarcopenia (the NUTRICOVID study), the prevalence and impact of dysphagia (the COVID-19-DN-OD study), or changes in corporal composition measured through nutritional ultrasound and bioimpedance analysis (the NUTRIECOMUSCLE study). In this article, the principal investigators of the three projects discuss the steps taken to develop these studies in the context of a worldwide pandemic: from initial concept, study design, and patient recruitment to problems in the execution of the project in day-to-day practice and publication policies. Also, they offer some insights on the initial results and the implications which these studies may have for current clinical practice.

Introducción: NutriCOVer es un programa de investigación impulsado por Nutricia a nivel global para apoyar iniciativas de investigación clínica en 16 países de todo el mundo. El programa tiene como objetivo adaptar el cuidado nutricional a las necesidades de los pacientes con COVID-19 dados de alta de la unidad de cuidados intensivos. En España se están desarrollando tres proyectos de investigación, siendo un país de referencia dentro del programa NutriCOVer. Estos estudios analizan la evolución de los pacientes tras una COVID-19 grave desde el punto de vista nutricional, evaluando aspectos relevantes como la prevalencia y evolución de la desnutrición y la sarcopenia (estudio NUTRICOVID), la prevalencia y el impacto de la disfagia (estudio COVID-19- DN-OD) y los cambios de la composición corporal medida por ecografía nutricional y bioimpedanciometría (estudio NUTRIECOMUSCLE). En este artículo, los investigadores que lideran estos tres proyectos discuten todos los pasos que han seguido para el desarrollo de los estudios en el contexto de una pandemia mundial: desde la idea inicial, el diseño y el reclutamiento de pacientes hasta los problemas de ejecución que se han encontrado en el día a día o la política de publicación de los resultados. Además, ofrecen algunas impresiones sobre los resultados iniciales y las implicaciones que pueden tener estos estudios para cambiar la práctica clínica habitual.

Phase angle and standardized phase angle from bioelectrical impedance measurements as a prognostic factor for mortality at 90 days in patients with COVID-19: A longitudinal cohort study.

BACKGROUND & AIMS: Severe acute COVID-19 has taken on pandemic proportions with growing interest in identification of prognostic factors for mortality. Standardized bioelectrical impedance (BI) phase angle (SPhA), which is PhA adjusted by age and sex, has been related to mortality in patients with several diseases but never investigated in COVID-19. Inflammation, a consequence of COVID-19 infection, affects fluid status (hydration) and can be identified with PhA. The aim of this study was to determine the predictive role of PhA on 90 days survival of adults with COVID-19. METHODS: We studied 127 consecutive patients diagnosed with COVID-19. BI measurements determined with a 50 kHz phase-sensitive BI device, body composition parameters and laboratory markers were evaluated as predictors of mortality. RESULTS: Non-surviving COVID-19 patients had significantly lower PhA and SPhA values (p < 0.001) and increased hydration (p < 0.001) compared to surviving patients. Patients in the lowest SPhA quartile had increased (p < 0.001) mortality and hospital stay, hyperhydration (p < 0.001), increased inflammation biomarkers [CRP (p < 0.001)], decreased nutritional parameters: body mass cell index [BCMI (p < 0.001) albumin (p < 0.001)], and reduced other biomarkers [D-dimer (p = 0.002)]. Multivariate analysis (Cox regression) revealed that PhA and hydration status, adjusted for age, sex, BMI, diabetes, hypertension, dyslipidaemia or heart disease, were associated (p < 0.001) with increased mortality. The hazard ratio was 2.48 (95% CI, 1.60-3.84, p < 0.001) for PhA and 1.12 (95% CI, 1.04-1.20, p = 0.003) for hydration percentage. PhA <3.95° was the cut-off for predicting mortality in acute COVID-19 with 93.8% sensitivity and 66.7% specificity. PhA offers greater sensitivity as a predictive prognostic test at admission, compared to the established analytical parameters of poor prognosis (CRP, lymphocytes, prealbumin). CONCLUSIONS: Low PhA (<3.95°), independent of age, sex, BMI, and comorbidities, is a significant predictor of mortality risk in COVID-19. These findings suggest that the evaluation of body composition with single-frequency phase-sensitive BI measurements should be included in the routine clinical assessment of COVID-19 patients at hospital admission to identify patients at increased mortality risk.