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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.

Gastrointestinal complications following on-pump cardiac surgery are orphan but serious risk factors for postoperative morbidity and mortality. We aimed to assess incidence, perioperative risk factors, treatment modalities and outcomes. A university medical center audit comprised 4883 consecutive patients (median age 69 [interquartile range IQR 60-76] years, 33% female, median logistic EuroScore 5 [IQR 3-11]) undergoing all types of cardiac surgery including surgery on the thoracic aorta; patients undergoing repair of congenital heart disease, implantation of assist devices or cardiac transplantation were excluded. Coronary artery disease was the leading indication for on-pump cardiac surgery (60%), patients undergoing cardiac surgery under urgency or emergency setting were included in analysis. We identified a total of 142 patients with gastrointestinal complications. To identify intra- and postoperative predictors for gastrointestinal complications, we applied a 1:1 propensity score matching procedure based on a logistic regression model. Overall, 30-day mortality for the entire cohort was 5.4%; the incidence of gastrointestinal complications was 2.9% and median time to complication 8 days (IQR 4-12). Acute pancreatitis (n = 41), paralytic ileus (n = 14) and acute cholecystitis (n = 18) were the leading pathologies. Mesenteric ischemia and gastrointestinal bleeding accounted for 16 vs. 18 cases, respectively. While 72 patients (51%) could be managed conservatively, 27 patients required endoscopic/radiological (19%) or surgical intervention (43/142 patients, 30%); overall 30-day mortality was 12.1% (p<0.001). Propensity score matching identified prolonged skin-to-skin times (p = 0.026; Odds Ratio OR 1.003, 95% Confidence Interval CI 1.000-1.007) and extended on-pump periods (p = 0.010; OR 1.006, 95%CI 1.001-1.011) as significant perioperative risk factors. Prolonged skin-to-skin times and extended on-pump periods are important perioperative risk factors regardless of preoperative risk factors.

Gastrointestinal motility disturbances in critically ill patients are frequent in the ICU setting, causing considerable discomfort and are associated with increased rates of morbidity and mortality. This review focuses on the pathophysiological basis of intestinal motility, the major patterns of pathological motility alterations, the impact on patient outcome, and current therapeutic options. Intestinal motility is controlled by the enteric nervous system, modulated by hormones and extrinsic afferent and efferent neurons. Pathological motility disturbances can affect the stomach, small bowel, and colon separately or in combination. Changes in esophageal motor activity contribute to the aspiration of gastric juice, whereas early enteral feeding most frequently fails due to gastric intolerance. Disturbances in digestive and interdigestive motility patterns and the inability to switch motor activity from the interdigestive to the digestive pattern also contribute to feeding disability and thus to increased morbidity and mortality as well. The therapeutic options for motility disturbances in critically ill patients include the adjustment of electrolyte imbalances, tailored fluid management, early enteral feeding, appropriate management of catecholamines and drugs used for analgosedation, and prokinetic drugs. Unfortunately, the therapeutic options for treating motility disturbances in ICU patients are still limited. This situation requires careful assessment of ICU patients with respect to gut motility disturbances and their pathophysiological mechanisms and an individually tailored treatment to prevent further aggravation of existing motility disturbances.

Background Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. Methods This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. Results Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. Conclusions Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.

A healthy woman with acute onset of pulmonary oedema and severely depressed left ventricular function underwent endomyocardial biopsy under the clinical suspicion of fulminant myocarditis. While awaiting the results of biopsy, the situation deteriorated to Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) and extracorporeal membrane oxygenation was implanted. Finally, immunohistochemistry in biopsy specimen corresponded to fulminant lymphocytic myocarditis, although active myocarditis was excluded. Furthermore, gene expression profiling identified giant cell myocarditis although multinuclear cells were absent. This prompted the start of immunosuppression with cortisone and cyclosporine. The patient fully recovered.

Cerulein and neostigmine are prokinetic drugs whose potency and effective dose range are barely known. The aim of this study was to assess their benefit for normal and compromised peristalsis. In vitro, isolated segments of guinea pig small intestine. Setting : University laboratory. Small bowel segments were mounted in tissue baths and luminally perfused with Tyrode solution. Test drugs (prokinetic: cerulein, neostigmine; inhibitory: atropine, hexamethonium, epinephrine, sufentanil) were added to the tissue bath. Peristalsis was quantified via changes in the peristaltic pressure threshold. One-way and two-way analysis of variance (ANOVA) were used for statistical analysis. Cerulein (0.03-100 nM) stimulated normal peristalsis in a concentration-dependent manner and reversed paralysis of peristalsis induced by all inhibitory test drugs to a similar extent. The properistaltic effect of neostigmine was limited to a narrow concentration range (0.03-0.1 micro M), whereas concentrations >0.3 micro M inhibited peristalsis. Neostigmine more effectively counteracted blockage of peristalsis caused by atropine than that caused by hexamethonium. The inhibitory effects of epinephrine and sufentanil on peristalsis were reversed only at the concentration range of 0.1-0.3 micro M neostigmine. Cerulein stimulates normal peristalsis in vitro at a wide concentration range and reverses blockage of peristalsis caused by drugs with a site of action either on the enteric nervous system or intestinal smooth muscle. Neostigmine's prokinetic effect, to the contrary, is limited to a small concentration range and best seen when peristalsis is depressed by blockage of cholinergic muscle activation.

Purpose To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness. Methods We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined “early” EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds. Results We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion. Conclusions We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.

Telemonitoring of patients with chronic heart failure (CHF) is an emerging concept to detect early warning signs of impending acute decompensation in order to prevent hospitalization. The goal of the MOBIle TELemonitoring in Heart Failure Patients Study (MOBITEL) was to evaluate the impact of home-based telemonitoring using Internet and mobile phone technology on the outcome of heart failure patients after an episode of acute decompensation. Patients were randomly allocated to pharmacological treatment (control group) or to pharmacological treatment with telemedical surveillance for 6 months (tele group). Patients randomized into the tele group were equipped with mobile phone-based patient terminals for data acquisition and data transmission to the monitoring center. Study physicians had continuous access to the data via a secure Web portal. If transmitted values went outside individually adjustable borders, study physicians were sent an email alert. Primary endpoint was hospitalization for worsening CHF or death from cardiovascular cause. The study was stopped after randomization of 120 patients (85 male, 35 female); median age was 66 years (IQR 62-72). The control group comprised 54 patients (39 male, 15 female) with a median age of 67 years (IQR 61-72), and the tele group included 54 patients (40 male, 14 female) with a median age of 65 years (IQR 62-72). There was no significant difference between groups with regard to baseline characteristics. Twelve tele group patients were unable to begin data transmission due to the inability of these patients to properly operate the mobile phone (\"never beginners\"). Four patients did not finish the study due to personal reasons. Intention-to-treat analysis at study end indicated that 18 control group patients (33%) reached the primary endpoint (1 death, 17 hospitalizations), compared with 11 tele group patients (17%, 0 deaths, 11 hospitalizations; relative risk reduction 50%, 95% CI 3-74%, P = .06). Per-protocol analysis revealed that 15% of tele group patients (0 deaths, 8 hospitalizations) reached the primary endpoint (relative risk reduction 54%, 95% CI 7-79%, P= .04). NYHA class improved by one class in tele group patients only (P< .001). Tele group patients who were hospitalized for worsening heart failure during the study had a significantly shorter length of stay (median 6.5 days, IQR 5.5-8.3) compared with control group patients (median 10.0 days, IQR 7.0-13.0; P= .04). The event rate of never beginners was not higher than the event rate of control group patients. Telemonitoring using mobile phones as patient terminals has the potential to reduce frequency and duration of heart failure hospitalizations. Providing elderly patients with an adequate user interface for daily data acquisition remains a challenging component of such a concept.

Atypical teratoid rhabdoid tumors (AT/RT) are characterized by a poor prognosis and a manifestation within the first 2 years of life. Genetic hallmark of these tumors is the homozygous inactivation of SMARCB1 or, in some rare cases, of SMARCA4. While heterozygous pathogenic variants of SMARCA4 have been described, inter alia, in the context of other CNS malignancies such as medulloblastoma or glioblastoma, the co-occurrence of pathogenic variants in both, SMARCB1 and SMARCA4, in the same AT/RT has to our knowledge not been reported previously. Liquid biopsy, a rapidly developing and promising technique measuring cell-free DNA (cfDNA) in body fluids such as the cerebrospinal fluid (CSF), offers a minimally invasive method to assess disease status. It has yet to be established as a standard procedure in the diagnostic workup of CNS tumors. We present the case of a three-year-old male diagnosed with an AT/RT that exhibits both biallelic alterations of SMARCB1 due to a frameshift mutation and loss of heterozygosity as well as a heterozygous missense variant in SMARCA4 presenting with early disease progression. We employed liquid biopsy successfully to monitor disease progression throughout treatment and the subsequent relapse. We highlight the ramifications that simultaneous alterations in two chromatin-modifying genes may have for tumor biology and clinical course.

Atypical teratoid/rhabdoid tumors (ATRT) are known for their heterogeneity concerning pathophysiology and outcome. However, predictive factors within distinct subgroups still need to be uncovered. Using multiplex immunofluorescent staining and single-cell RNA sequencing we unraveled distinct compositions of the immunological tumor microenvironment (TME) across ATRT subgroups. CD68 + cells predominantly infiltrate ATRT-SHH and ATRT-MYC and are a negative prognostic factor for patients’ survival. Within the murine ATRT-MYC and ATRT-SHH TME, Cd68 + macrophages are core to intercellular communication with tumor cells. In ATRT-MYC distinct tumor cell phenotypes express macrophage marker genes. These cells are involved in the acquisition of chemotherapy resistance in our relapse xenograft mouse model. In conclusion, the tumor cell-macrophage interaction contributes to ATRT-MYC heterogeneity and potentially to tumor recurrence.