Organ Dysfunction

This study aims to better understand 3 crucial questions: 1. Why do some patients experience more severe complications after heart surgery than others? 2. Are there markers on our genetic makeup (called epigenetic modifications) that can predict complications after major surgery? 3. How do epigenetic modifications lead to overactive inflammation that causes harm to patients after heart surgery? Over 270,000 patients undergo major surgery in Scotland each year. Major surgery is associated with increased risk of complications, particularly in older patients with multiple health conditions. Complications are a leading cause of death, delayed recovery, long-term illness and increased healthcare cost to the NHS. Significant complications occur in up to 57% of patients after heart surgery. In response to major surgery, the body stimulates an inflammatory response as part of a complex repair mechanism, however, in some cases inflammation can become exaggerated, becoming harmful and contributing to the development of complications. The investigators believe that a patient's risk of overactive inflammation, which can lead to complications after surgery, is heavily influenced by a patient-specific system of biological markers, layered upon their DNA; a scientific field known as epigenetics. Where a patient's DNA (their 'genetics') may be considered as an instruction manual for each cell's molecular processes, these 'epigenetic' markers work as if someone has highlighted sections of the manual to be read (and actioned). The pattern of these markers on immune system cells can therefore dictate the extent of the inflammatory response, especially after a major insult such as surgery. While the DNA itself cannot be modified, epigenetic markers can be modified, through strategies including diet, exercise, and medication. The aim of this study is to evaluate whether the modifiable epigenetic code of key immune-system cells dictates the extent of post-operative inflammation, contributing to organ damage and complications. With patients' permission, the investigators will: 1. Obtain blood samples before and after major heart surgery, to test for epigenetic markers and inflammation. 2. Observe patients after surgery and collect routine data from laboratory tests and patient observations which assess for organ dysfunction and inflammation. 3. Conduct patient questionnaires before and after surgery to assess physical fitness and patient-centred quality of life measures. 4. Analyse patterns between patients who have severe organ dysfunction after surgery and those patients who have minimal organ dysfunction after similar surgery, to better understand which patients are at greatest risk, according to their epigenetic makeup. This study may improve understanding of which patients are likely to suffer organ damage and complications after major surgery, and which patients may have a protective epigenetic makeup which reduces complications. With this knowledge, the investigators aim is that future patients could receive personalised treatment plans before surgery, to modify their epigenetic makeup, reduce harm from complications and improve outcomes for patients. The investigators are not testing any new treatments in this study.

Acute pancreatitis may cause early respiratory, cardiovascular, or renal dysfunction and may require intensive care and organ support. Thoracic epidural analgesia may improve pain control, reduce systemic opioid exposure, and facilitate gastrointestinal recovery; however, its effect on overall organ support burden remains uncertain. This is a single-center, prospective, randomized, open-label, parallel-group clinical trial. A total of 150 adults with acute pancreatitis within 72 hours of symptom onset and early respiratory, cardiovascular, or renal dysfunction will be randomized in a 1:1 ratio to receive either ropivacaine-only thoracic epidural analgesia plus standard care or standardized conventional analgesia plus standard care. The primary outcome is alive and organ support-free days through day 14 after randomization. Secondary and exploratory outcomes include alive and organ support-free days through day 28, organ dysfunction-free days, ventilator-free days, renal replacement therapy-free days, vasoactive drug-free days, 28-day mortality, pain scores, systemic opioid exposure, gastrointestinal and nutritional outcomes, intra-abdominal pressure, inflammatory markers, complications, length of stay, hospital costs, and adverse events related to thoracic epidural analgesia.

The study will compare ICU sub-units, those with additional support of a clinician awareness system, ICU Beacon, and those receiving the standard of care. The win-ratio composite outcome will be assessed by comparing patients by study group and stratified by APACHE score at admission.

The goal of this observational study is to develop and evaluate an organ dysfunction score adapted to pregnancy and early puerperium (SOFA-OBS) that also incorporates a non-invasive tool to evaluate respiratory function (pulse oximeter). The main question it aims to answer is: Does an organ dysfunction score adapted to pregnant and postpartum patients have a higher capacity to predict mortality than a non-adjusted organ dysfunction score? Participants: Patients requiring ICU (Intensive Care Units) admission, who are either pregnant or postpartum (up to 3 days after giving birth). The investigators aimed to include 130 participants. The investigators will only collect participants' data and laboratory results that ICU doctor usually need for clinical practice. No additional interventions are required. Moreover, the investigators will evaluate if measuring participants' oxygenation through a non-invasive tool (pulse oximeter) is equally effective as measuring oxygenation by an arterial puncture. Background: When managing severely ill patients in ICU, the investigators often use what it is called scores. Scores refer to a numerical value assigned to a patient's condition, which often predict outcome. The Sequential Organ Failure Assessment (SOFA) score is a scoring system that assess severity of organ dysfunction (in liver, kidney, blood pressure, respiratory, neurologic and platelets). It also identifies patients with severe infections (sepsis) and patients with bad outcomes. Patients undergoing pregnancy or early postpartum develop physiological changes, such us a decrease in creatinine (a laboratory test measuring kidney function) and a decrease in blood pressure during the second trimester. These changes are not considered by the SOFA score. Actually, there is not an organ dysfunction score adapted to pregnant/postpartum patients to be used in the ICU. Moreover, a blood sample taken by arterial puncture is required to evaluate respiratory function by the SOFA score, which is a painful procedure. Instead, the investigators could evaluate respiratory function using a pulse oximeter, which measures peripheral oxygen saturation without needing an arterial puncture. Potential benefits: A SOFA-OBS would hopefully become a more precise tool than general SOFA to evaluate organ dysfunction and to predict outcome among these patients. It would also help to detect sepsis earlier and treat it promptly, which might help reducing its mortality.

This multicenter, randomized controlled trial aims to evaluate whether early initiation of supplemental parenteral nutrition (SPN) (on day 4 of ICU admission) compared to late initiation (on day 8) can reduce 28-day all-cause mortality in critically ill patients. Secondary objectives include assessing the effects of early SPN on long-term functional outcomes (2-year EQ-5D-5L scores), mortality at various timepoints (ICU, 28-day, 90-day, 180-day, and 2-year), ICU length of stay, serum prealbumin levels (days 8 and 28), skeletal muscle measurements (diaphragm thickness, biceps, quadriceps, and rectus femoris cross-sectional area), incidence of ICU-acquired infections, adverse events (e.g., hyperglycemia, hypoglycemia, dyslipidemia, liver dysfunction), and ventilator-free days within 28 days. Eligible patients are adults (≥18 years) with at least one organ failure (SOFA score ≥2) within 24 hours of ICU admission, expected to remain in the ICU for \>72 hours, and unable to reach 50% of caloric target via enteral nutrition (EN) within the first 72 hours. A total of 946 patients will be enrolled and randomized to receive either early SPN (day 4) or late SPN (day 8) in addition to standard EN. Follow-up will include in-hospital assessments and telephone follow-ups at 28, 90, 180 days, and 2 years. The study hypothesizes that early SPN may improve short-term survival and nutritional/muscle status, though its impact on long-term quality of life remains to be determined.