Longitudinal changes in global structural brain connectivity and cognitive performance in former hospitalized COVID-19 survivors: an exploratory study.

BACKGROUND: Long-term sequelae of COVID-19 can result in reduced functionality of the central nervous system and substandard quality of life. Gaining insight into the recovery trajectory of admitted COVID-19 patients on their cognitive performance and global structural brain connectivity may allow a better understanding of the diseases' relevance. OBJECTIVES: To assess whole-brain structural connectivity in former non-intensive-care unit (ICU)- and ICU-admitted COVID-19 survivors over 2 months following hospital discharge and correlate structural connectivity measures to cognitive performance. METHODS: Participants underwent Magnetic Resonance Imaging brain scans and a cognitive test battery after hospital discharge to evaluate structural connectivity and cognitive performance. Multilevel models were constructed for each graph measure and cognitive test, assessing the groups' influence, time since discharge, and interactions. Linear regression models estimated whether the graph measurements affected cognitive measures and whether they differed between ICU and non-ICU patients. RESULTS: Six former ICU and six non-ICU patients completed the study. Across the various graph measures, the characteristic path length decreased over time (ß = 0.97, p = 0.006). We detected no group-level effects (ß = 1.07, p = 0.442) nor interaction effects (ß = 1.02, p = 0.220). Cognitive performance improved for both non-ICU and ICU COVID-19 survivors on four out of seven cognitive tests 2 months later (p < 0.05). CONCLUSION: Adverse effects of COVID-19 on brain functioning and structure abate over time. These results should be supported by future research including larger sample sizes, matched control groups of healthy non-infected individuals, and more extended follow-up periods.

Antibiotic prescriptions in the context of suspected bacterial respiratory tract superinfections in the COVID-19 era: a retrospective quantitative analysis of antibiotic consumption and identification of antibiotic prescription drivers.

This study aims to quantify antibiotic consumption for suspected respiratory tract superinfections in COVID-19 patients, while investigating the associated drivers of antibiotic prescribing in light of the current signs of antibiotic overuse. Adult patients with a positive COVID-19 diagnosis admitted to a Belgian 721-bed university hospital were analyzed retrospectively (March 11th-May 4th, 2020), excluding short-term admissions (< 24 h). Antibiotic prescriptions were analyzed and quantified, using Defined Daily Doses (DDD) per admission and per 100 bed days. Possible drivers of antibiotic prescribing were identified by means of mixed effects logistic modelling analysis with backwards selection. Of all included admissions (n = 429), 39% (n = 171) were prescribed antibiotics for (presumed) respiratory tract superinfection (3.6 DDD/admission; 31.5 DDD/100 bed days). Consumption of beta-lactamase inhibitor-penicillin combinations was the highest (2.55 DDD/admission; 23.3 DDD/100 bed days). Four drivers were identified: fever on admission (OR 2.97; 95% CI 1.42-6.22), lower SpO2/FiO2 ratio on admission (OR 0.96; 95% CI 0.92-0.99), underlying pulmonary disease (OR 3.04; 95% CI 1.12-8.27) and longer hospital stay (OR 1.09; 95% CI 1.03-1.16). We present detailed quantitative antibiotic data for presumed respiratory tract superinfections in hospitalized COVID-19 patients. In addition to knowledge on antibiotic consumption, we hope antimicrobial stewardship programs will be able to use the drivers identified in this study to optimize their interventions in COVID-19 wards.

[Experiences of COVID-ICU-survivors: mixed-methods study of psychological consequences by written survey]. / Ervaringen van patiënten die COVID-ic-opname overleefden: enquête naar psychische gevolgen.

BACKGROUND: In the coming years, mental health care may come into contact with patients who developed psychological complaints related to their critical illness and stay in the intensive care unit (ICU) as a result of COVID-19. However, the experiences of these patients are to date rarely documented. AIM: Gaining insight into the experiences of COVID-ICU-survivors. METHODS 19 COVID-ICU survivors answered a written survey four months after admission. Screening lists measured psychological complaints and sleeping disorders. Visual analogue scales (VAS) measured the influence of the pandemic context and the quality of life. A written survey mapped patient experiences. Quantitative data were analyzed descriptively and qualitative data by means of thematic analysis. RESULTS: 50% of the participants experienced psychological complaints or sleeping disorders. A limited social network and media coverage of COVID-19 complicated the recovery process of patients. 19% of the participants experienced a reduced quality of life. A weak social network caused feelings of hopelessness. Still, patients showed great resilience. CONCLUSION: Most COVID-ICU survivors are resilient enough to integrate their experiences into their lives, despite the challenges the pandemic context poses on their rehabilitation. It is therefore important not to overmedicalise psychological complaints that occur during rehabilitation. Our attention needs to be directed to those with a weak social network.

TICACOS international: A multi-center, randomized, prospective controlled study comparing tight calorie control versus Liberal calorie administration study.

Since the first TICACOS study, 3 additional studies have been published comparing a medical nutrition therapy guided by indirect calorimetry to a regimen prescribed on the basis of predictive equations. A recent guidelines document included a meta-analysis including these 4 papers and found a trend for improvement (OR 0.98-1.48) in favor of medical nutrition therapy guided by indirect calorimetry in terms of survival. The aim of our study was to perform a multicenter prospective, randomized, controlled non blinded study in critically patients to assess the added value for measuring daily resting energy expenditure as a guide for nutritional support. The primary objective was to decrease infectious rate of these critically ill patients. MATERIAL AND METHODS: This phase III, multi-center, randomized, controlled non blinded study was planned to include 580 newly-admitted, adult ventilated ICU patients that were planned to stay more than 48 h in the ICU departments. The nutritional support was aimed to meet 80-100% of energy requirement measured by indirect calorimetry. The calorie needs were determined by IC in the Study group and by an equation (20-25 kcal/kg ideal body weight/day) in the Control Group. The ICU staff was trained to strive to supply 80-100% of a patient's energy requirements through artificial nutrition, preferably enteral feeding. Primary endpoint was infection rate and secondary endpoints included other morbidities and mortality during ICU, at 90 and 180 days. Comparison between the study and the control group was performed using T test for equality of means (independent samples test). Correlations were performed using the Pearson correlation test. A p level of 0.05 or below was considered as significant. Cross tabs procedure used Chi-square test for testing differences in complication rates, length of stay and length of ventilation. Correlations between energy balances and complications was also be tested using one way analysis as well as ANOVA analysis between groups and within groups. Kaplan Meir curves assessed the proportion of surviving patients in the 2 groups. RESULTS: Seven centers with a calorimeter available participated to the study. Due to slow inclusion rate, the study was stopped after 6 years and after inclusion of 417 patients only. From the 417 intended to treat patients, 339 followed the protocol. There was no differences between control and study groups in terms of age, sex BMI, SOFA (7.1 ± 3.1 vs 7.4 ± 3.3) and APACHE II scores (22.4 ± 7.9 vs 22.2 ± 7.4). The rate of infection (40 vs 31), including pneumonia rate, need for surgery, dialysis requirement, length of ventilation, ICU length of stay, and hospital length of stay were not different between groups. Mortality (30 in the control vs 21 in the study group) was not significantly different between groups. The decreased mortality observed in the study group when added to previous studies may have a positive effect on the meta-analysis previously published. CONCLUSION: Tight Calorie Control guided by indirect calorimetry decreased the rate of infection and mortality but not significantly. This may be explained by the not relatively small sample size. There results together with the previous 4 prospective randomized studies, may improve the results of the meta-analysis exploring the effects of IC guided nutrition on mortality.

MECCIAS trial: Metabolic consequences of continuous veno-venous hemofiltration on indirect calorimetry.

BACKGROUND: and aims: Caloric prescription based on resting energy expenditure (REE) measured with indirect calorimetry (IC) improves outcome and is the gold standard in nutritional therapy of critically ill patients. Until now continuous renal replacement therapy (CRRT) precluded the use of IC due to several mechanisms. We investigated the impact of CRRT on V̇CO2, V̇O2 and REE to facilitate indirect calorimetry during CRRT. METHODS: In 10 critically ill ventilated patient in need of continuous veno-venous hemofiltration (CVVH) using citrate predilution we performed IC in 4 different states: baseline, high dose, baseline with NaCl predilution and without CVVH. CO2 content of effluent fluid was measured by a point of care blood gas analyzer. Carbon dioxide production (V̇CO2) measured with IC was adapted by adding the CO2 flow of effluent and deducing CO2 flow in postdilution fluid to calculate a true V̇CO2. True REE was calculated with the Weir equation using the true V̇CO2. RESULTS: CO2 removal in effluent during baseline, high dose and NaCl predilution was respectively 24 mL/min, 38 mL/min and 23 mL/min. Together with the CO2 delivery by the postdilution fluid this led to an adaptation of REE respectively by 34 kcal/d or 2% (p = 0,002), 44 kcal/d or 3% (p = 0,002) and 33 kcal/d or 2% (p = 0,002). Compared to the true REE during baseline of 1935 ± 921 kcal/d, true REE during high dose was 1723 ± 752 kcal/d (p = 0.65), during NaCl predilution it was 1604 ± 633 kcal/d (p = 0.014) and without CRRT it was 1713 ± 704 kcal/d (p = 0.193). CONCLUSIONS: CO2 alterations due to CVVH are clinically of no importance so no correction factor of REE is needed with or without CVVH. IC must be performed during CVVH as CVVH seems to alter metabolism. These changes may be mainly explained by the use of citrate predilution.

Energy expenditure and caloric targets during continuous renal replacement therapy under regional citrate anticoagulation. A viewpoint.

BACKGROUND: Indirect calorimetry (IC) is the gold standard for measuring energy expenditure in critically ill patients However, continuous renal replacement therapy (CRRT) is a formal contraindication for IC use. AIMS: To discuss specific issues that hamper or preclude an IC-based assessment of energy expenditure and correct caloric prescription in CRRT-treated patients. METHODS: Narrative review of current literature. RESULTS: Several relevant pitfalls for validation of IC during CRRT were identified. First, IC measures CO2 production (VCO2) and O2 consumption to calculate resting energy expenditure (REE) with the Weir equation. VCO2 measurements are influenced by CRRT because CO2 is exchanged during the blood purification process. CO2 exchange also depends on type of pre- and/or postdilution fluid(s). CO2 dissolves in different forms with dynamic but unpredictable impact on VCO2. Second, the effect of immunologic activation and heat loss on REE caused by extracorporeal circulation during CRRT is poorly documented. Third, caloric prescription should be adapted to CRRT-induced in- and efflux of different nutrients. Finally, citrate, which is the preferred anticoagulant for CRRT, is a caloric source that may influence IC measurements and REE. CONCLUSION: Better understanding of CRRT-related processes is needed to assess REE and provide individualized nutritional therapy in this condition.

Measuring resting energy expenditure during extracorporeal membrane oxygenation: preliminary clinical experience with a proposed theoretical model.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with severe respiratory failure. Indirect calorimetry (IC) is a safe and non-invasive method for measuring resting energy expenditure (REE). No data exist on the use of IC in ECMO-treated patients as oxygen uptake and carbon dioxide elimination are divided between mechanical ventilation and the artificial lung. We report our preliminary clinical experience with a theoretical model that derives REE from IC measurements obtained separately on the ventilator and on the artificial lung. METHODS: A patient undergoing veno-venous ECMO for acute respiratory failure due to bilateral pneumonia was studied. The calorimeter was first connected to the ventilator and oxygen consumption (VO2 ) and carbon dioxide transport (VCO2 ) were measured until steady state was reached. Subsequently, the IC was connected to the membrane oxygenator and similar gas analysis was performed. VO2 and VCO2 values at the native and artificial lung were summed and incorporated in the Weir equation to obtain a REEcomposite . RESULTS: At the ventilator level, VO2 and VCO2 were 29.5 ml/min and 16 ml/min. VO2 and VCO2 at the artificial lung level were 213 ml/min and 187 ml/min. Based on these values, a REEcomposite of 1703 kcal/day was obtained. The Faisy-Fagon and Harris-Benedict equations calculated a REE of 1373 and 1563 kcal/day. CONCLUSION: We present IC-acquired gas analysis in ECMO patients. We propose to insert individually obtained IC measurements at the native and the artificial lung in the Weir equation for retrieving a measured REEcomposite .

Measured versus calculated resting energy expenditure in critically ill adult patients. Do mathematics match the gold standard?

BACKGROUND: Indirect calorimetry (IC) is considered to be the standard method for estimating energy requirements in intensive care unit (ICU) patients. Hence, most ICU clinicians still rely on various mathematical formulas to calculate caloric requirements in their patients. We assessed whether measurements obtained by IC reached agreement with the results of such commonly used equations. METHODS: Retrospective study in consecutively hospitalized patients in a mixed medico-surgical adult ICU. Resting energy expenditure (REE) was measured by IC in all patients as a standard procedure within our routine nutritional care planning and simultaneously calculated from 10 distinct predictive equations. IC was performed with the VmaxTM Encore 29n calorimeter (VIASYS Healthcare Inc, Yorba Linda, CA). Bland-Altman plots and regression analysis were used to assess agreement between measured and calculated REE. RESULTS: The study included 259 critically ill patients: 161 subjects (62%) met final analysis criteria (age 63 ± 16 years; 58% males). Measured REE was 1571 ± 423.5 kcal/24 h with VO2 0.23 ± 0.06 L/min and VCO2 0.18 ± 0.05 L/min. Calculated values correlated very weakly with IC-derived measurements. Only the Swinamer equation and the Penn State 2010 reached an R² > 0.5. Widely used formulas in daily ICU practice such as the adjusted Harris Benedict, Faisy-Fagon, and ESICM '98 statement equations, reached R² values of respectively only 0.44, 0.49, and 0.41. Calculation resulted in under- as well as overestimation of REE. Global formulas reached no acceptable correlation in elderly or obese critically ill patients. CONCLUSION: In critically ill adult patients, measured REE poorly correlated with calculated values, regardless what formula was used. Our findings underscore the important role of IC to adequately estimate energy requirements in this particularly frail population.

Facing acid-base disorders in the third millennium - the Stewart approach revisited.

Acid-base disorders are common in the critically ill. Most of these disorders do not cause harm and are self-limiting after appropriate resuscitation and management. Unfortunately, clinicians tend to think about an acid-base disturbance as a "disease" and spend long hours effectively treating numbers rather than the patient. Moreover, a sizable number of intensive-care physicians experience difficulties in interpreting the significance of or understanding the etiology of certain forms of acid-base disequilibria. Traditional tools for interpreting acid-base disorders may not be adequate for analyzing the complex nature of these metabolic abnormalities. Inappropriate interpretation may also lead to wrong clinical conclusions and incorrectly influence clinical management (eg, bicarbonate therapy for metabolic acidosis in different clinical situations). The Stewart approach, based on physicochemical principles, is a robust physiological concept that can facilitate the interpretation and analysis of simple, mixed, and complex acid-base disorders, thereby allowing better diagnosis of the cause of the disturbance and more timely treatment. However, as the concept does not attach importance to plasma bicarbonate, clinicians may find it complicated to use in their daily clinical practice. This article reviews various approaches to interpreting acid-base disorders and suggests the integration of base-excess and Stewart approach for a better interpretation of these metabolic disorders.

Recovery of muscular performance after surgical stress in elderly patients.

INTRODUCTION: Inflammation is related to muscle wasting in elderly persons. Since surgery is accompanied by an important inflammatory response, the degree of muscle wasting and related symptoms such as weakness and tiredness might exacerbate very rapidly in elderly surgery patients. METHODS: PubMed and Web of Science were systematically screened for articles reporting the influence of surgery-induced inflammation on muscle performance and/or fatigue in elderly patients. Studies reporting surgery-induced inflammation and changes in muscle performance and/or fatigue, but without analyzing their association were excluded. Although 5 relevant articles were identified including older patients (highest ages reported were 71-92 years), none focused exclusively on elderly patients. Only 2 studies assessed muscle performance, and in none muscle mass was evaluated. Overall, we found evidence that in elderly patients higher surgery-induced inflammation was significantly related to worse muscle performance and fatigue in the first postoperative days as well as after more than one month (especially for fatigue) following the intervention. Pre-operative anti-inflammatory treatment using steroids or glucocorticoids can reduce the surgery-induced inflammatory response and improve the recovery of muscle performance and postoperative fatigue in elderly elective abdominal surgery or arthroplasty patients. CONCLUSION: We can conclude that to date, only few studies have investigated the association between surgery-induced inflammation and changes in postoperative muscle performance and fatigue in elderly patients. More research is warranted focusing on both the short -and long-term effects of surgical stress on muscle performance in elderly patients as well as the on risks and benefits of peri-operative anti-inflammatory treatment.

Phosphate induced crystal acute kidney injury - an under-recognized cause of acute kidney injury potentially leading to chronic kidney disease: case report and review of the literature.

Acute phosphate nephropathy or nephrocalcinosis is a tubulointerstitial nephropathy characterized by tubular calcium phosphate deposition - crystal nephropathy - and slowly progressive renal insufficiency during or following treatment with preparations containing sodium phosphate. We report a patient who developed nephrocalcinosis (crystal induced acute kidney injury) following the administration of a combination of oral and rectal sodium phosphate for treatment of postoperative constipation. A timely renal replacement therapy procedure may reverse the process of crystallization and the irreversible slope towards chronic dialysis.

New insights regarding rationale, therapeutic target and dose of hemofiltration and hybrid therapies in septic acute kidney injury.

Mediator removal from tissue (capillary blood compartment, CABC) and transport to the central circulation (central blood compartment, CEBC) must be effective. Effectiveness through a passive mechanism seems unlikely as the surface of CEBC (30 m(2)) is smaller than CABC (300 m(2)) whereby the former will be a limiting factor in passive transport. According to studies, a high exchange volume can induce an 80-fold increase in lymphatic flow. This results in displacement (active transport) of mediators to CEBC. Recent studies have shown that the delivered dose constitutes the mainstay of continuous renal replacement therapy. However, these results are not likely to change the recommendation: 35 ml/kg/h, adjusted for predilution, in septic acute kidney injury (AKI). Recently, studies were focusing on global intensive care unit AKI. In non-septic AKI, those studies show that 20-25 ml/kg/h was optimal. The DO-RE-MI trial underscored the importance of delivery which could be obtained by targeting doses between 5 and 10 ml/kg/h higher than prescribed. Until the IVOIRE trial becomes available, septic AKI should be treated by continuous veno-venous hemofiltration at 35 ml/kg/h. In non-septic AKI, 25 ml/kg/h remains optimal.

Septic acute kidney injury: the culprit is inflammatory apoptosis rather than ischemic necrosis.

For a long time, acute kidney injury (AKI) was considered to be a primarily hemodynamic condition characterized by a reduction of renal blood flow, induced by either cardiogenic or distributive (septic) shock. Consequently, all efforts to treat AKI were essentially concentrated on increasing renal flow by enhancing cardiac flow output and perfusion pressure. At the beginning of this decade, Bellomo and co-workers produced new and intriguing data in an animal model of septic AKI that undermined existing concepts. They observed that medullar and cortical renal blood flow were both maintained and even increased in septic shock, underscoring that septic AKI was a totally different physiological phenomenon than nonseptic AKI. Also, apoptosis was found to play a more important role in sepsis and septic shock than pure necrosis. Despite these findings, the role of apoptosis as a main mechanism of organ dysfunction remains topic of debate.

A genomic-based approach identifies FXYD domain containing ion transport regulator 2 (FXYD2)gammaa as a pancreatic beta cell-specific biomarker.

AIMS/HYPOTHESIS: Non-invasive imaging of the pancreatic beta cell mass (BCM) requires the identification of novel and specific beta cell biomarkers. We have developed a systems biology approach to the identification of promising beta cell markers. METHODS: We followed a functional genomics strategy based on massive parallel signal sequencing (MPSS) and microarray data obtained in human islets, purified primary rat beta cells, non-beta cells and INS-1E cells to identify promising beta cell markers. Candidate biomarkers were validated and screened using established human and macaque (Macacus cynomolgus) tissue microarrays. RESULTS: After a series of filtering steps, 12 beta cell-specific membrane proteins were identified. For four of the proteins we selected or produced antibodies targeting specifically the human proteins and their splice variants; all four candidates were confirmed as islet-specific in human pancreas. Two splice variants of FXYD domain containing ion transport regulator 2 (FXYD2), a regulating subunit of the Na(+)-K(+)-ATPase, were identified as preferentially present in human pancreatic islets. The presence of FXYD2gammaa was restricted to pancreatic islets and selectively detected in pancreatic beta cells. Analysis of human fetal pancreas samples showed the presence of FXYD2gammaa at an early stage (15 weeks). Histological examination of pancreatic sections from individuals with type 1 diabetes or sections from pancreases of streptozotocin-treated Macacus cynomolgus monkeys indicated a close correlation between loss of FXYD2gammaa and loss of insulin-positive cells. CONCLUSIONS/INTERPRETATION: We propose human FXYD2gammaa as a novel beta cell-specific biomarker.

Surgery-induced inflammation in relation to age, muscle endurance, and self-perceived fatigue.

BACKGROUND: Elective abdominal surgery can be considered as a model for an important acute inflammatory trigger in human participants. The aim of the study was to explore the effect of surgery-induced inflammation on muscle strength, endurance, and self-perceived fatigue and its relation with age. METHODS: Sixty-six elective abdominal surgery patients aged 24-91 years were assessed before and at the second and fourth day after surgical intervention. Outcome parameters were grip strength, muscle endurance, fatigue subscale of the Profile of Mood State and visual analog scale for pain, and the circulating inflammatory mediators C-reactive protein, interleukin (IL)-6, and tumor necrosis factor-alpha (TNF-alpha). RESULTS: All parameters worsened postoperatively (p < .01) and remained significantly (p < .05) worse until the fourth day postsurgery, except for TNF-alpha (no significant change). Older age was related to higher surgery-induced IL-6 levels at the second (p < .05) and fourth postoperative (p < .01) day and to worse self-perceived fatigue and muscle endurance (both p < .05) at the fourth postoperative day. Higher pain levels at the second day following surgery was related to more self-perceived fatigue (p < .05). Worsening muscle endurance following surgery was significantly related to higher IL-6 release following surgery (p < .01) and self-perceived fatigue (p < .05) at the fourth day following the intervention. Age and surgery-induced increase in circulating IL-6 at Day 4 postsurgery was highest in patients showing both worsened muscle endurance and self-perceived fatigue (p < .05). CONCLUSIONS: Surgery-induced inflammation is related to reduced muscle endurance and the sensation of fatigue. Elderly patients suffer from a higher impact of surgery on muscle endurance.

Magnetic resonance cholangiopancreatography in the preoperative assessment of patients with biliary pancreatitis.

BACKGROUND: The ultimate treatment of acute biliary pancreatitis (ABP) is undoubtedly laparoscopic cholecystectomy, but controversy remains about the optimal imaging method in the preoperative assessment of these patients. In this study, we evaluated the usefulness of magnetic resonance cholangiopancreatography (MRCP) in detecting common bile duct (CBD) stones and associated pathologies in patients with ABP. At the same time, we tried to determine the natural transit time of gallstones from gallbladder to duodenum in ABP. METHODS: Between February 1999 and October 2006 a prospective observational study was conducted and 104 consecutive patients with ABP were recruited. MRCP findings were correlated with subsequent endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, intraoperative cholangiography or clinical follow-up. RESULTS: MRCP correctly predicted the presence of CBD stones in 19 out of 104 patients, and there were two false-positive and four false-negative results. The ability of MRCP to detect CBD stones was: positive predictive value 90.5%, negative predictive value 95.2%, sensitivity 82.6%, specificity 97.5% and overall accuracy 94.2%. MRCP performed within 48 h after admission showed CBD stones in 28.6% of the patients decreasing to 8.0% after 1 week. MRCP disclosed cholecystitis in 25 patients, anatomical variants of the cystic duct in 10 patients and a wide variety of other abnormalities of the upper abdominal cavity. CONCLUSION: MRCP is highly accurate in the preoperative detection of CBD stones and other biliopancreatic pathologies in patients with gallstone pancreatitis.