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Purpose Acute gastrointestinal (GI) dysfunction and failure have been increasingly recognized in critically ill patients. The variety of definitions proposed in the past has led to confusion and difficulty in comparing one study to another. An international working group convened to standardize the definitions for acute GI failure and GI symptoms and to review the therapeutic options. Methods The Working Group on Abdominal Problems (WGAP) of the European Society of Intensive Care Medicine (ESICM) developed the definitions for GI dysfunction in intensive care patients on the basis of the available evidence and current understanding of the pathophysiology. Results Definitions for acute gastrointestinal injury (AGI) with its four grades of severity, as well as for feeding intolerance syndrome and GI symptoms (e.g. vomiting, diarrhoea, paralysis, high gastric residual volumes) are proposed. AGI is a malfunctioning of the GI tract in intensive care patients due to their acute illness. AGI grade I = increased risk of developing GI dysfunction or failure (a self-limiting condition); AGI grade II = GI dysfunction (a condition that requires interventions); AGI grade III = GI failure (GI function cannot be restored with interventions); AGI grade IV = dramatically manifesting GI failure (a condition that is immediately life-threatening). Current evidence and expert opinions regarding treatment of acute GI dysfunction are provided. Conclusions State-of-the-art definitions for GI dysfunction with gradation as well as management recommendations are proposed on the basis of current medical evidence and expert opinion. The WGAP recommends using these definitions for clinical and research purposes.

In the past decades, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has been applied to a broad range of biological samples, e.g., forensics and preclinical samples. The use of MALDI-MSI for the analysis of bone tissue has been limited due to the insulating properties of the material but more importantly the absence of a proper sample preparation protocol for undecalcified bone tissue. Undecalcified sections are preferred to retain sample integrity as much as possible or to study the tissue-bone bio interface in particular. Here, we optimized the sample preparation protocol of undecalcified bone samples, aimed at both targeted and untargeted applications for forensic and preclinical applications, respectively. Different concentrations of gelatin and carboxymethyl cellulose (CMC) were tested as embedding materials. The composition of 20% gelatin and 7.5% CMC showed to support the tissue best while sectioning. Bone tissue has to be sectioned with a tungsten carbide knife in a longitudinal fashion, while the sections need to be supported with double-sided tapes to maintain the morphology of the tissue. The developed sectioning method was shown to be applicable on rat and mouse as well as human bone samples. Targeted (methadone and EDDP) as well as untargeted (unknown lipids) detection was demonstrated. DHB proved to be the most suitable matrix for the detection of methadone and EDDP in positive ion mode. The limit of detection (LOD) is estimated to approximately 50 pg/spot on bone tissue. The protocol was successfully applied to detect the presence of methadone and EDDP in a dosed rat femur and a dosed human clavicle. The best matrices for the untargeted detection of unknown lipids in mouse hind legs in positive ion mode were CHCA and DHB based on the number of tissue-specific peaks and signal-to-noise ratios. The developed and optimized sample preparation method, applicable on animal and human bones, opens the door for future forensic and (pre)clinical investigations.

Hip fractures in elderly patients significantly reduce independence and quality of life. Early postoperative gait performance remains poorly understood, particularly regarding differences between surgical treatments, such as proximal femur nailing and hemiarthroplasty. Identifying gait alterations early in rehabilitation could optimize clinical interventions. This prospective observational cohort study included 40 elderly patients hospitalized after acute hip fracture surgery. Relative peak force and step duration were assessed using the ambulant pressure biofeedback system during postoperative mobilization. Additionally, three-dimensional gait analysis evaluated spatiotemporal parameters and sagittal plane kinematics of the hip, knee, and ankle. Results demonstrated significant improvements in median peak force (45.32% to 70.00%, (p < 0.001)) and median step duration (2.96 s to 137 s, (p < 0.001)) at the end of the hospitalization period. No significant differences in step duration and peak force were observed between the different surgical procedures, proximal femur nail, and hemiarthroplasty. Three-dimensional gait analysis showed significantly reduced hip extension during terminal stance in the operated leg compared to the healthy leg. These findings highlight the utility of biofeedback systems for monitoring early rehabilitation progress and emphasize the importance of 3D gait analysis in identifying early postoperative gait deficits. Targeted interventions during hospitalization could enhance functional recovery and improve patient outcomes.

Background Perturbation-based balance training (PBT) is an emerging intervention shown to improve balance recovery responses and reduce falls in everyday life in older adults. However, perturbation interventions were heterogeneous in nature and need improvement. This study aims to investigate the effects of a PBT protocol that was designed to address previously identified challenges of PBT, in addition to usual care, on balance control and fear of falling in older adults at increased risk of falling. Methods Community-dwelling older adults (age ≥ 65 years) who visited the hospital outpatient clinic due to a fall incident were included. Participants received PBT in addition to usual care (referral to a physiotherapist) versus usual care alone. PBT consisted of three 30-minute sessions in three weeks. Unilateral treadmill belt accelerations and decelerations and platform perturbations (shifts and tilts) were applied during standing and walking on the Computer Assisted Rehabilitation Environment (CAREN, Motek Medical BV). This dual-belt treadmill embedded in a motion platform with 6 degrees of freedom is surrounded by a 180° screen on which virtual reality environments are projected. Duration and contents of the training were standardised, while training progression was individualised. Fear of falling (FES-I) and balance control (Mini-BESTest) were assessed at baseline and one week post-intervention. Primary analysis compared changes in outcome measures between groups using Mann-Whitney U tests. Results Eighty-two participants were included (PBT group n = 39), with a median age of 73 years (IQR 8 years). Median Mini-BESTest scores did not clinically relevantly improve and were not significantly different between groups post-intervention (p = 0.87). FES-I scores did not change in either group. Conclusions Participation in a PBT program including multiple perturbation types and directions did not lead to different effects than usual care on clinical measures of balance control or fear of falling in community-dwelling older adults with a recent history of falls. More research is needed to explore how to modulate PBT training dose, and which clinical outcomes are most suitable to measure training effects on balance control. Trial registration Nederlands Trial Register NL7680. Registered 17-04-2019 – retrospectively registered. https://www.trialregister.nl/trial/7680 .

PurposeTraumatic brain injury (TBI) and chest trauma are common injuries in severely injured patients. Both entities are well known to be associated with severe post-traumatic complications, including pneumonia, a common complication with a significant impact on the further clinical course. However, the relevance of TBI, chest trauma and particularly their combination as risk factors for the development of pneumonia and its impact on outcomes are not fully elucidated.MethodsA retrospective analysis of poly-traumatized patients treated between 2010 and 2015 at a level I trauma centre was performed. Inclusion criteria were: Injury Severity Score ≥ 16 and age ≥ 18 years. TBI and chest trauma were classified according to the Abbreviated Injury Scale. Complications (i.e. acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS) and pneumonia) were documented by a review of the medical records. The primary outcome parameter was in-hospital mortality.ResultsOver the clinical course, 19.9% of all patients developed pneumonia, and in-hospital mortality was 25.3%. Pneumonia (OR 5.142, p = 0.001) represented the strongest independent predictor of in-hospital mortality, followed by the combination of chest injury and TBI (OR 3.784, p = 0.008) and TBI (OR 3.028, p = 0.010). Chest injury alone, the combination of chest injury and TBI, and duration of ventilation were independent predictors of pneumonia [resp. OR 4.711 (p = 0.004), OR 4.193 (p = 0.004), OR 1.002 (p < 0.001)].ConclusionsChest trauma alone and especially its combination with TBI represent high-risk injury patterns for the development of pneumonia, which forms the strongest predictor of mortality in poly-traumatized patients.

Background Esophageal surgery is associated with complications and mortality. It is highly important to develop tools predicting unfavorable postoperative outcome. Esophageal cancer and neoadjuvant chemoradiotherapy (CRT) induce skeletal muscle wasting, which leads to diminished physiologic reserves. The purpose of this study was to investigate whether the degree of muscle mass lost during neoadjuvant CRT predicts postoperative mortality. Methods A total of 123 consecutive patients undergoing surgery for esophageal malignancy in the period 2008–2012 were included, of whom 114 received neoadjuvant CRT. Skeletal muscle mass was measured on routinely performed CT scans by assessing L3 muscle index (according to the Prado method) before and after neoadjuvant CRT, and the amount of muscle mass lost during neoadjuvant CRT (muscle loss index) was calculated. It was investigated whether this amount was associated with postoperative 30-day or in-hospital mortality and morbidity. Results In the complete cohort, no significant association between loss of muscle mass and mortality was found. However, skeletal muscle mass was significantly lower in patients with stage III–IV tumors compared with stage I–II tumors, prior to neoadjuvant CRT. In the stage III–IV subgroup, the amount of muscle mass lost during neoadjuvant CRT was predictive of postoperative mortality: −13.5 % (standard deviation 6.2 %) in patients who died postoperatively compared with −5.0 % (standard deviation 8.3 %) in surviving patients, p  = 0.02. Conclusions Measurement of muscle mass loss during neoadjuvant chemoradiotherapy may provide a readily available and inexpensive assessment to identify patients at risk for developing unfavorable postoperative outcome after resection of esophageal malignancies, especially in patients with stage III–IV tumors.

The need for an artificial scaffold in very large bone defects is clear, not only to limit the risk of graft harvesting but also to improve clinical success. The use of custom osteoconductive scaffolds made from biodegradable polyester and ceramics can be a valuable patient-friendly option, especially in case of a concomitant infection. Multiple types of scaffolds for the Masquelet procedure (MP) are available. However, these frequently demonstrate central graft involution when defects exceed a certain size and the complication rates remain high. This paper describes three infected tibial defect nonunions with a segmental defect over 10 centimeters long treated with a three-dimensional (3D)-printed polycaprolactone-tricalcium phosphate (PCL-TCP) cage in combination with biological adjuncts. Three male patients, between the ages of 37 and 47, were treated for an infected tibial defect nonunion after sustaining Gustilo grade 3 open fractures. All had a segmental midshaft bone defect of more than 10 centimeters (range 11-15cm). First-stage MPs consisted of extensive debridement, external fixation, and placement of anterior lateral thigh flaps. Positive cultures were obtained from all patients during this first stage, which were treated with specific systemic antibiotics for 12 weeks. The second-stage MP was carried out at least two months after the first stage. CT scans were obtained after the first stage to manufacture defect-specific cages. In the final procedure, a custom 3D-printed PCL-TCP cage (Osteopore, Singapore) was placed in the defect in combination with biological adjuncts (BMAC, RIA-derived autograft, iFactor, and BioActive Glass). Bridging of the defect, assessed at six months by CT, was achieved in all cases. SPECT scans six months post-operatively demonstrated active bone regeneration, also involving the central part of the scaffold. All three patients regained function and reported less pain with full weight bearing. This case report shows that 3D-printed PCL-TCP cages in combination with biological adjuncts are a novel addition to the surgical treatment of very large bone defects in (infected) post-traumatic nonunion of the tibia. This combination could overcome some of the current drawbacks in this challenging indication.

Protein turnover in skeletal muscle tissue is highly responsive to nutrient intake in healthy adults. To provide a comprehensive overview of post-prandial protein handling, ranging from dietary protein digestion and amino acid absorption, the uptake of dietary protein derived amino acids over the leg, the post-prandial stimulation of muscle protein synthesis rates, to the incorporation of dietary protein derived amino acids in de novo muscle protein. 12 healthy young males ingested 20 g intrinsically [1-13C]-phenylalanine labeled protein. In addition, primed continuous L-[ring-2H5]-phenylalanine, L-[ring-2H2]-tyrosine, and L-[1-13C]-leucine infusions were applied, with frequent collection of arterial and venous blood samples, and muscle biopsies throughout a 5 h post-prandial period. Dietary protein digestion, amino acid absorption, splanchnic amino acid extraction, amino acid uptake over the leg, and subsequent muscle protein synthesis were measured within a single in vivo human experiment. 55.3±2.7% of the protein-derived phenylalanine was released in the circulation during the 5 h post-prandial period. The post-prandial rise in plasma essential amino acid availability improved leg muscle protein balance (from -291±72 to 103±66 μM·min-1·100 mL leg volume-1; P<0.001). Muscle protein synthesis rates increased significantly following protein ingestion (0.029±0.002 vs 0.044±0.004%·h-1 based upon the muscle protein bound L-[ring-2H5]-phenylalanine enrichments (P<0.01)), with substantial incorporation of dietary protein derived L-[1-13C]-phenylalanine into de novo muscle protein (from 0 to 0.0201±0.0025 MPE). Ingestion of a single meal-like amount of protein allows ~55% of the protein derived amino acids to become available in the circulation, thereby improving whole-body and leg protein balance. About 20% of the dietary protein derived amino acids released in the circulation are taken up in skeletal muscle tissue following protein ingestion, thereby stimulating muscle protein synthesis rates and providing precursors for de novo muscle protein synthesis. trialregister.nl 3638.

This study investigated whether there are differences in the composition of the cutaneous microbiome of the unaffected skin between patients with pressure ulcers compared with those without pressure ulcers. The cutaneous microbiome of the unaffected skin of 15 patients with sacral pressure ulcers compared to 15 patients without pressure ulcers was analysed. It demonstrated that the inter-individual variation in skin microbiota of patients with pressure ulcers was significantly higher (P = 0.01). The abundance of 23 species was significantly different with Staphylococcus aureus and unclassified Enterococcus the most abundant species in patients with pressure ulcers. Random Forest models showed that eight species were associated with pressure ulcers occurrence in 81% of the patients. A subset of four species gave the strongest interaction. The presence of unclassified Enterococcus had the highest association with pressure ulcer occurrence. This study is the first to demonstrate that the cutaneous microbiome is altered in patients with pressure ulcers.

Over the last 3 decades, scientific evidence advocates an association between traumatic brain injury (TBI) and accelerated fracture healing. Multiple clinical and preclinical studies have shown an enhanced callus formation and an increased callus volume in patients, respectively, rats with concomitant TBI. Over time, different substances (cytokines, hormones, etc.) were in focus to elucidate the relationship between TBI and fracture healing. Until now, the mechanism behind this relationship is not fully clarified and a consensus on which substance plays the key role could not be attained in the literature. In this review, we will give an overview of current concepts and opinions on this topic published in the last decade and both clinical and pathophysiological theories will be discussed.