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Background and Aims The incidence of frailty is increasing as the population ages, which has important clinical implications given the associations between frailty and poor outcomes in the bladder cancer population. Due to a multi-organ system decline and decreased physiologic reserve, frail patients are vulnerable to stressors of disease and have poorer mortality and morbidity rates than their nonfrail peers. The association between frailty and poor outcomes has been documented across multiple populations, including radical cystectomy, creating a need for frailty assessments to be used preoperatively for risk stratification. We aim to provide a review of the common frailty assessments and their relevance to radical cystectomy patients. Findings A variety of assessments for frailty exist, from short screening items to comprehensive geriatric assessments. The syndrome spans multiple organ systems, as do the potential diagnostic instruments. Some instruments are less practical for use in clinical practice by urologists, such as the Canadian Study of Health and Aging Frailty Index and Comprehensive Geriatric Assessment. The tool most studied in radical cystectomy is the modified Frailty Index, associated with high grade complications and 30-days mortality. Frailty often coexists with malnutrition and sarcopenia, stressing the importance of screening for and addressing these syndromes to improve patient's perioperative outcomes. Conclusions There is no universally agreed upon frailty assessment, but the most studied in radical cystectomy is the modified Frailty Index, providing valuable data with which to counsel patients preoperatively. Alterations in immune phenotypes provide potential future diagnostic biomarkers for frailty.

COVID-19 is a syndrome that includes more than just isolated respiratory disease, as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) also interacts with the cardiovascular, nervous, renal, and immune system at multiple levels, increasing morbidity in patients with underlying cardiometabolic conditions and inducing myocardial injury or dysfunction. Emerging evidence suggests that patients with the highest rate of morbidity and mortality following SARS-CoV2 infection have also developed a hyperinflammatory syndrome (also termed cytokine release syndrome). We lay out the potential contribution of a dysfunction in autonomic tone to the cytokine release syndrome and related multiorgan damage in COVID-19. We hypothesize that a cholinergic anti-inflammatory pathway could be targeted as a therapeutic avenue. Graphical Abstract .

PURPOSE OF REVIEW: Survivorship or addressing impaired quality of life (QoL) in ICU survivors has been named 'the defining challenge of critical care' for this century to address this challenge; in addition to optimal nutrition, we must learn to employ targeted metabolic/muscle assessment techniques and utilize structured, progressive ICU rehabilitative strategies. RECENT FINDINGS: Objective measurement tools such as ccardiopulmonary exercise testing (CPET) and muscle-specific ultrasound show great promise to assess/treat post-ICU physical dysfunction. CPET is showing that systemic mitochondrial dysfunction may underlie development and persistence of poor post-ICU functional recovery. Finally, recent data indicate that we are poor at delivering effective, early ICU rehabilitation and that there is limited benefit of currently employed later ICU rehabilitation on ICU-acquired weakness and QoL outcomes. SUMMARY: The combination of nutrition with effective, early rehabilitation is highly likely to be essential to optimize muscle mass/strength and physical function in ICU survivors. Currently, technologies such as muscle-specific ultrasound and CPET testing show great promise to guide ICU muscle/functional recovery. Further, we must evolve improved ICU-rehabilitation strategies, as current methods are not consistently improving outcomes. In conclusion, we must continue to look to other areas of medicine and to athletes if we hope to ultimately improve 'ICU Survivorship'.

Volume recruitment from the splanchnic compartment is an important physiological response to stressors such as physical activity and blood loss. In the setting of heart failure (HF), excess fluid redistribution from this compartment leads to increased cardiac filling pressures with limitation in exercise capacity. Recent evidence suggests that blocking neural activity of the greater splanchnic nerve (GSN) could have significant benefits in some patients with heart failure (HF) by reducing cardiac filling pressures and improvement in exercise capacity. However, to date the long-term safety of splanchnic nerve modulation (SNM) in the setting of HF is unknown. SNM is currently used in clinical practice to alleviate some forms of chronic abdominal pain. A systematic review of series where permanent SNM was used as a treatment for chronic abdominal pain indicates that permanent SNM is well tolerated, with side-effects limited to transient diarrhea or abdominal colic and transient hypotension. The pathophysiological role of the GSN in volume redistribution, the encouraging findings of acute and chronic pilot SNM studies and the safety profile from permanent SNM for pain provides a strong basis for continued efforts to study this therapeutic target in HF.

Iatrogenic malnutrition and underfeeding are ubiquitous in intensive care units (ICUs) worldwide for prolonged periods after ICU admission. A major driver leading to the lack of emphasis on timely ICU nutrition delivery is lack of objective data to guide nutrition care. If we are to ultimately overcome current fundamental challenges to effective ICU nutrition delivery, we must all adopt routine objective, longitudinal measurement of energy targets via indirect calorimetry (IC). Key evidence supporting the routine use of IC in the ICU includes (1) universal societal ICU nutrition guidelines recommending IC to determine energy requirements; (2) data showing predictive equations or body weight calculations that are consistently inaccurate and correlate poorly with measured energy expenditure, ultimately leading to routine overfeeding and underfeeding, which are both associated with poor ICU outcomes; (3) recent development and worldwide availability of a new validated, accurate, easy-to-use IC device; and (4) recent data in ICU patients with coronavirus disease 2019 (COVID-19) showing progressive hypermetabolism throughout ICU stay, emphasizing the inaccuracy of predictive equations and marked day-to-day variability in nutrition needs. Thus, given the availability of a new validated IC device, these findings emphasize that routine longitudinal IC measures should be considered the new standard of care for ICU and post-ICU nutrition delivery. As we would not deliver vasopressors without accurate blood pressure measurements, the ICU community is only likely to embrace an increased focus on the importance of early nutrition delivery when we can consistently provide objective IC measures to ensure personalized nutrition care delivers the right nutrition dose, in the right patient, at the right time to optimize clinical outcomes.

PURPOSE OF REVIEW: Intensive Care Unit (ICU) survivors frequently suffer significant, prolonged physical disability. ‘ICU Survivorship’, or addressing quality of life impairments post-ICU care, is a defining challenge, and existing standards of care fail to successfully address these disabilities. We suggest addressing persistent catabolism by treatment with testosterone analogs combined with structured exercise is a promising novel intervention to improve “ICU Survivorship”. RECENT FINDINGS: One explanation for lack of success in addressing post-ICU physical disability is most ICU patients exhibit severe testosterone deficiencies early in ICU that drives persistent catabolism despite rehabilitation efforts. Oxandrolone is an FDA-approved testosterone analogue for treating muscle weakness in ICU patients. A growing number of trials with this agent combined with strutured exercise show clinical benefit, including improved physical function and safety in burns and other catabolic states. However, no trials of oxandrolone/testosterone and exercise in non-burn ICU populations have been conducted. SUMMARY: Critical illness leads to a catabolic state, including severe testosterone deficiency that persists throughout hospital stay, and results in persistent muscle weakness and physical dysfunction. The combination of an anabolic agent with adequate nutrition and structured exercise is likely essential to optimize muscle mass/strength and physical function in ICU survivors. Further research in ICU populations is needed.

Recent research suggested an important role for pulmonary extracellular adenosine triphosphate (ATP) in the development of ventilation-induced lung injury. This injury is induced by mechanical deformation of alveolar epithelial cells, which in turn release ATP to the extracellular space. Measuring extracellular ATP in exhaled breath condensate (EBC) may be a non-invasive biomarker for alveolar deformation. Here, we study the feasibility of bedside ATP measurement in EBC. We measured ATP levels in EBC in ten subjects before and after an exercise test, which increases respiratory parameters and alveolar deformation. EBC lactate concentrations were measured as a dilution marker. We found a significant increase in ATP levels in EBC (before 73 RLU [IQR 50–209] versus after 112 RLU [IQR 86–203]; p value 0.047), and the EBC ATP-to-EBC lactate ratio increased as well (p value 0.037). We present evidence that bedside measurement of ATP in EBC is feasible and that ATP levels in EBC increase after exercise. Future research should measure ATP levels in EBC during mechanical ventilation as a potential biomarker for alveolar deformation.

Given all its systemic adaptive requirements, pregnancy shares several features with physical exercise. In this pilot study, we aimed to assess the physiological response to submaximal cardiopulmonary exercise testing (CPET) in early pregnancy. In 20 healthy, pregnant women (, The response to a cardiopulmonary exercise test is already altered in the first trimester of pregnancy. Pregnant women show a slower hemodynamic recovery and an excessive ventilatory response to submaximal exercise.

IntroductionThe importance of cardiovascular health in relation to pregnancy outcome is increasingly acknowledged. Women who develop certain pregnancy complications, in particular preeclampsia, are at higher risk for future cardiovascular disease. Independent of its outcome, pregnancy requires a substantial adaptive response of the maternal cardiovascular system. In the Hemodynamic Adaptation to Pregnancy and Placenta-related Outcome (HAPPO) study, we aim to examine longitudinal maternal haemodynamic adaptation to pregnancy from the preconception period onwards. We hypothesise that women who will develop adverse pregnancy outcomes have impaired cardiovascular health before conception, leading to haemodynamic maladaptation to pregnancy and diminished uteroplacental vascular development.Methods and analysisIn this prospective cohort study embedded in the Rotterdam periconception cohort, 200 women with a history of placenta-related pregnancy complications (high-risk group) and 100 women with an uncomplicated obstetric history (low-risk group) will be included. At five moments (preconception, first, second and third trimester and postdelivery), women will undergo an extensive examination of the macrocirculatory and microcirculatory system and uteroplacental vascular development. The main outcome measures are differences in maternal haemodynamic adaptation to pregnancy between women with and without placenta-related pregnancy complications. In a multivariate linear mixed model, the relationship between maternal haemodynamic adaptive parameters, (utero)placental vascularisation indices and clinical outcomes (occurrence of pregnancy complications, embryonic and fetal growth trajectories, miscarriage rate, gestational age at delivery, birth weight) will be studied. Subgroup analysis will be performed to study baseline and trajectory differences between high-risk and low-risk women, independent of subsequent pregnancy outcome.Ethics and disseminationThis study protocol was approved by the Medical Ethics Committee of the Erasmus MC, Rotterdam, the Netherlands (MEC 2018–150). Results will be disseminated to the medical community by publications in peer-reviewed journals and presentations at scientific congresses. Also, patient associations will be informed and the public will be informed by dissemination through (social) media.Trial registration numberNL7394 (www.trialregister.nl)

PURPOSE OF REVIEW: As many as 2 of every 3 major surgery patients are malnourished preoperatively – a diagnosis rarely made and treated even less frequently. Unfortunately, perioperative malnutrition is perhaps the least often identified surgical risk factor and is among the most treatable to improve outcomes. RECENT FINDINGS: Two important perioperative nutrition guidelines were published recently. Both emphasize nutrition assessment as an essential component of preoperative screening. The recently published Perioperative Nutrition Screen (PONS) readily identifies patients at malnutrition risk, allowing for preoperative nutritional optimization. The use of CT scan and ultrasound lean body mass (LBM) evaluation to identify sarcopenia associated with surgical risk and guide nutrition intervention is garnering further support. Preoperative nutrition optimization in malnourished patients, use of immunonutrition in all major surgery, avoidance of preoperative fasting, inclusion of post-operative high-protein nutritional supplements, and early postoperative oral intake have all recently been shown to improve outcomes and should be utilized. SUMMARY: The recent publication of new surgical nutrition guidelines, the PONS score and use of LBM assessments will allow better identification and earlier intervention on perioperative malnutrition. It is essential that in the future no patient undergoes elective surgery without nutrition screening and nutrition intervention when malnutrition risk is identified.

Purpose of reviewTo help guide metabolic support in critical care, an understanding of patients’ nutritional status and risk is important. Several methods to monitor lean body mass are increasingly used in the ICU and knowledge about their advantages and limitations is essential.Recent findingsComputed tomography scan analysis, musculoskeletal ultrasound, and bioelectrical impedance analysis are emerging as powerful clinical tools to monitor lean body mass during ICU stay. Accuracy, expertise, ease of use at the bedside, and costs are important factors, which play a role in determining, which method is most suitable. Exciting new research provides an insight into not only quantitative measurements, but also qualitative measurements of lean body mass, such as infiltration of adipose tissue and intramuscular glycogen storage.SummaryMethods to monitor lean body mass in the ICU are under constant development, improving upon bedside usability and offering new modalities to measure. This provides clinicians with valuable markers with which to identify patients at high nutritional risk and to evaluate metabolic support during critical illness.