Clinical Research Directory

PF-Organized Corticosteroid-Associated Heterogeneity in Sepsis

This retrospective multicohort observational study evaluates whether the PaO2/FiO2 ratio (P/F ratio) organizes heterogeneity in the association between early systemic corticosteroid exposure and mortality among critically ill patients with sepsis. The study uses one internal critical-care cohort (ICCA) and two external critical-care databases (MIMIC and eICU). Analyses include internal discovery, broad external testing, reconstruction of external cohorts toward vasopressor-anchored shock-decision contexts, realized-exposure observational analyses, and strategy-level analyses using a simplified clone-censor-weighting framework (Lite-CCW). The primary objective is to characterize whether corticosteroid-associated outcome patterns differ across P/F strata and whether similar directional patterns are observed across independent ICU datasets after decision-context reconstruction. The study is hypothesis-generating and does not assign corticosteroid treatment or define a clinical treatment-selection rule.

Combined Predictive Value of RSBI and CALLY Index in Predicting Weaning Success in ICU Patients

The primary objective of this prospective observational study is to evaluate the effectiveness of combining the Rapid Shallow Breathing Index (RSBI) and CRP-Albumin-Lymphocyte (CALLY) index to predict weaning success in adult patients within the intensive care unit. While weaning from mechanical ventilation is a critical clinical step, existing physiological metrics like RSBI do not fully capture a patient's inflammatory or nutritional status. This research introduces the CALLY index calculated as the ratio of the patient's immuno-nutritional reserve (Albumin and Lymphocytes) to systemic inflammation (CRP) as a complementary metabolic marker. By tracking approximately 105 participants at Basaksehir Cam and Sakura City Hospital, the study monitors weaning success over both a 48 hour and a 7 day period to identify both immediate and late phase extubation failures. The ultimate goal is to provide a more holistic prediction model that potentially reduces re-intubation rates and improves clinical outcomes by accurately identifying the optimal time for ventilator removal.

Lactate/Albumin Ratio and Mortality in Respiratory Failure

This retrospective observational study aims to evaluate the association between the lactate-to-albumin ratio (LAR) measured at ICU admission and 28-day mortality in adult patients admitted to the intensive care unit with acute respiratory failure. The study will also compare the prognostic value of LAR with that of existing clinical and laboratory parameters.

Respiratory Physiotherapy and Inflammatory Biomarkers in Critically Ill Patients With Pneumonia

The goal of this observational study is to evaluate the safety and impact of a protocolized respiratory physiotherapy program on the dynamics of systemic inflammatory biomarkers (procalcitonin \[PCT\] and C-reactive protein \[CRP\]) in critically ill adult patients with pneumonia in the intensive care unit (ICU), compared with standard medical care. The main questions it aims to answer are: Does a protocolized respiratory physiotherapy program accelerate the decline of PCT and CRP levels in critically ill patients with pneumonia compared to standard care? What is the incidence and safety profile of adverse events (e.g., transient desaturation, hemodynamic instability, or mechanical displacement) associated with respiratory physiotherapy sessions? Researchers will compare a prospective cohort receiving structured respiratory physiotherapy against a historical control group receiving standard care to determine changes in inflammatory trajectories and ICU length of stay. Participants in the prospective intervention group will: * Receive an individualized, protocolized respiratory physiotherapy regimen (including high-frequency chest wall oscillation \[HFCWO\], intrapulmonary acoustic percussion, positive expiratory pressure \[PEP\], and/or inspiratory muscle training \[IMT\]) tailored to their clinical deficits. * Undergo continuous safety monitoring during and up to 30 minutes following each physiotherapy session. * Have serum PCT and CRP levels measured at baseline (T0), Day 3 (T1), Day 7 (T2), and at ICU discharge (T3).

PICU Up!: A Pilot Stepped-wedge Trial of a Multicomponent Early Mobility Intervention for Critically Ill Children

Recent decreases in Pediatric Intensive Care Unit (PICU) mortality rates have been offset by increased morbidity and length of stay for vulnerable young patients. Heavy sedation, bedrest, and delirium contribute to a PICU culture of immobility. While studies in adult ICU patients demonstrate the clinical benefits of early mobilization, fewer than 25% of critically ill children mobilize early in the children's PICU stay. The investigators have demonstrated the safety and feasibility of the 'PICU Up!' Mobility Program, which integrates sleep promotion, delirium prevention, sedation optimization as a bundle to increase mobilization. However, the generalizability and broader impact on patient- and family-centered outcomes is unknown. Therefore, there is an urgent need for trials that blend both clinical effectiveness and implementation research to create a PICU culture of mobility and improve the value of PICU care. The overall objective of the proposed research is to determine the impact of a transdisciplinary and multifaceted early mobility program on clinical outcomes and ICU-acquired morbidities in critically ill children. Additionally, the investigators will identify barriers and facilitators to high-performance bundle adoption.

Abdominal Massage and Range-of-motion Exercise in Enterally Fed ICU Patients With Pressure Injuries

The purpose of this study is to evaluate whether two nursing interventions, lower abdominal massage and range-of-motion (ROM) exercises (gentle movements of the arm and leg joints), affect the healing of pressure injuries (bed sores) in intensive care patients who are fed through a tube (enteral nutrition). Intensive care patients often stay in bed for long periods and are at high risk of pressure injuries. Adequate nutrition is important for wound healing, but tube-fed patients often have digestive problems such as constipation, vomiting, bloating, or food remaining in the stomach, which can interrupt feeding. The main question this study will address is: Compared with routine care, do lower abdominal massage or ROM exercises affect digestive tolerance, nutritional markers, and pressure injury healing in tube-fed intensive care patients? The researchers hypothesize that lower abdominal massage may reduce digestive problems and support uninterrupted feeding, and that ROM exercises may support circulation and tissue healing. Both effects may, in turn, support pressure injury healing. Adult patients who have a pressure injury and receive enteral nutrition in the intensive care units of a state hospital in Türkiye will be randomly assigned to one of three groups: * Group 1: lower abdominal massage in addition to routine care * Group 2: ROM exercises in addition to routine care * Control group: routine care only The interventions will be applied for 15 minutes once a day for 7 days. Digestive tolerance (bowel movements, gastric residual volume, nausea, vomiting, abdominal distension), serum albumin, and pressure injury healing (Pressure Ulcer Scale for Healing, PUSH) will be monitored daily. Detailed Description This is a three-arm, parallel-group, randomized controlled experimental study planned for the intensive care units of a secondary-level state hospital in Türkiye. Patients who meet the eligibility criteria will be allocated to lower abdominal massage, ROM exercise, or routine care using a computer-generated randomization list (Microsoft Excel). The sample size will be calculated with G\*Power before data collection (planned minimum: 90 patients; effect size 0.20, alpha 0.05, 95% confidence level). Interventions: Lower abdominal massage (15 minutes: superficial effleurage, palm petrissage, fingertip vibration, closing effleurage; clockwise along the colon, with hands warmed in liquid paraffin) will be performed by an intensive care nurse. ROM exercises (flexion-extension, abduction-adduction and rotation of the upper and lower limb joints, with the patient supine; 3 repetitions per movement, held 30 seconds at the point of resistance; 15 minutes in total) will be performed after the researchers receive ROM training from a physiotherapist. The control group will receive routine intensive care only (nasogastric tube position checks, monitoring of gastric residual volume, defecation, nausea and vomiting, daily Braden Scale assessment, two-hourly repositioning, and stage-appropriate topical wound care). Data will be collected daily at 10:00 using a Patient Information Form and an Intervention/Control Group Patient Monitoring Form. Gastric residual volume will be assessed between 02:00 and 04:00 when feeding is paused. Planned analysis: Normality will be assessed with skewness and kurtosis values (±3). Between-group comparisons will use chi-square/Fisher's exact test, one-way ANOVA or Kruskal-Wallis test with post hoc tests. Within-group changes over time will use repeated-measures ANOVA, Friedman test, or Cochran's Q test as appropriate (significance p\<0.05).

Effectiveness of Virtual Reality in Improving Upper Limb Function in Critically Ill Patients

Millions of people are hospitalized every year in Intensive Care Units (ICUs) with severe health conditions due to various causes and categories of diseases, such as stroke, Traumatic Brain Injuries (TBI), polytrauma, sepsis, and others. In recent years, there has been a remarkable increase in survival rates among patients from all diagnostic categories admitted to the ICU. However, the stay of critically ill patients in the ICU is associated with a significant reduction in physical activity, even in cases where patients can participate in an active, voluntary rehabilitation program. This prolonged immobility has been linked to the development of Intensive Care Unit-Acquired Weakness (ICU-AW) and a decline in health-related quality of life (HRQOL). During the performance of Activities of Daily Living (ADLs), eye-hand coordination plays a crucial role. It depends on the integration of multiple brain systems and is therefore often impaired in many pathological conditions. Moreover, in recent years, the use of exercises that simulate functional tasks and activities of daily living, has been continuously increasing in physiotherapy and occupational therapy programs. Additionally, the implementation of purposeful, repetitive activity in patients with central nervous system lesions (e.g., stroke, traumatic brain injury) can lead to significant neuroplastic changes in the brain that may help improve upper limb function. Nowadays, Virtual Reality (VR) applications are increasingly used in patient rehabilitation. However, the application of fully immersive virtual reality devices for purposeful activities aiming to improve upper limb function in critically ill patients is an innovative intervention that has not yet been sufficiently studied to inform the development of Clinical Guidelines. Furthermore, despite its clinical significance, eye-hand coordination is not routinely assessed , and there is a limited amount of data regarding its rehabilitation, especially through VR technology. The aim of this study, therefore, is to investigate the effect of fully immersive virtual reality on the rehabilitation of sensorimotor perception and visuomotor coordination skills, as well as on the improvement of upper limb function in critically ill patients.

Adverse Events During Physical Therapy in Neurocritical ICU Patients

The goal of this observational study is to identify the clinical, neurological, hemodynamic, and respiratory variables associated with the occurrence of adverse events during physical therapy interventions in adult neurocritical patients admitted to the Intensive Care Unit (ICU). The main questions it aims to answer are: What clinical, neurological, hemodynamic, and respiratory factors are associated with adverse events during physical therapy in neurocritical patients? What is the incidence and type of adverse events that occur most frequently during physical therapy in this patient population? Researchers will compare clinical and physiological data between patients who experienced adverse events during physical therapy and those who did not, to determine risk factors associated with these complications. Participants' data will be retrospectively collected from medical records without performing new clinical interventions.

Humidification Effects on Airway Complications and Clinical Outcomes in Trauma ICU Patients on Mechanical Ventilation

This study compares the effects of two primary airway humidification methods-active heated humidifiers (HHs) and passive heat-and-moisture exchangers (HMEs)-on trauma intensive care unit (ICU) patients requiring prolonged mechanical ventilation. Adequate humidification is essential during mechanical ventilation because artificial airways bypass the body's natural ability to warm and moisten inhaled air. While existing guidelines show no overall superiority of one method over the other in general ICU populations, trauma patients present unique challenges, such as thick or bloody secretions, which may lead to airway obstructions and affect the performance of these devices. The main purpose of this randomized controlled trial is to evaluate how active versus passive humidification impacts airway complications (such as secretion viscosity and tube obstruction) and clinical outcomes (including ventilator-associated pneumonia, duration of mechanical ventilation, length of ICU stay, and mortality rates). A total of 162 adult trauma patients at Assiut University Hospital will be randomly assigned to either the HH group or the HME group to determine if there are significant clinical differences between the two methods in this specific patient population.

Metabolic and Functional Study of γδ T Cells in Critically Ill Patients

This prospective observational cohort study investigates the subset-specific metabolic adaptation and functional remodeling of cytotoxic γδ T cells in critically ill patients with and without sepsis. As a bridge between innate and adaptive immunity, γδ T cells contribute to early antimicrobial defense; however, their cytotoxic function and its metabolic regulation in sepsis remain incompletely understood. Our preliminary single-cell transcriptomic analysis revealed altered expression of cytotoxicity-associated genes (GZMB, PRF1, and GNLY) and mitochondrial oxidative phosphorylation (OXPHOS) pathway genes in cytotoxic γδ T cells from patients with sepsis. In particular, COX6C expression correlated with cytotoxic effector gene expression. Across healthy volunteers, critically ill non-septic patients, and critically ill septic patients, we will integrate flow cytometry, mitochondrial function assays, and functional validation experiments to characterize circulating cytotoxic γδ T-cell abundance and function and examine the contribution of COX6C to mitochondrial dysfunction and impaired cytotoxicity. To investigate the relationship between systemic tryptophan metabolism and these cellular abnormalities, targeted tryptophan-pathway metabolomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) will quantify kynurenic acid (KYNA), tryptophan, kynurenine, and related metabolites in paired peripheral blood and fecal samples. Patients with sepsis will be stratified into older (≥65 years) and non-older (\<65 years) groups and compared with age-matched healthy volunteers, with critically ill non-septic patients providing an additional disease control group. Metabolite concentrations and pathway-related ratios will be analyzed in relation to cytotoxic γδ T-cell abundance, cytotoxic function, mitochondrial OXPHOS, and COX6C expression, accounting for renal function, disease severity, antibiotic exposure, and nutritional support. These analyses will assess whether age-associated alterations in tryptophan metabolism, particularly KYNA, are associated with cytotoxic γδ T-cell dysfunction and identify candidate metabolic mechanisms for subsequent validation.

Effect of Lactiplantibacillus Plantarum DAD-13 on Inflammatory Markers in ICU Sepsis Patients

This study investigated whether giving the probiotic Lactiplantibacillus plantarum DAD-13 to sepsis patients in the intensive care unit (ICU) could help reduce inflammation and improve bowel function. A total of 30 adult ICU patients with sepsis were randomly assigned to receive either the probiotic or a placebo for four days, along with standard treatment. Blood tests were performed to measure inflammatory markers, including procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6), before and after the treatment. The study also observed defecation frequency and stool consistency. Results showed a clinical trend toward lower inflammation levels in the probiotic group and significantly better bowel function. The findings suggest that this probiotic may support immune response and gut health in sepsis patients, although more research is needed to confirm these results.

Individualised Blood Pressure Targets Versus Standard Care Among Critically Ill Patients With Shock

Aim The aim of the proposed RCT is to determine effectiveness of a strategy, where MAP (mean arterial blood pressure) targets during vasopressor therapy for shock in ICU are individualized based on patients' own pre-illness MAP that would be derived as an average of up to five most recent pre-illness blood pressure readings. Hypothesis We hypothesize that targeting a patient's pre-illness MAP during management of shock can minimize the degree of MAP-deficit (a measure of relative hypotension), which may help reduce the risk of 14-day mortality and major adverse kidney events by day 14 in ICU. Endpoints The primary endpoint will be the all-cause mortality rate at day 14. Secondary endpoints will be the time to death through day 14 and day 90, major adverse kidney events (MAKE-14), renal replacement therapy (RRT) free days until day 28, and 90-day all-cause mortality. Significance To date no major RCT has tested this strategy among ICU patients with shock. This pivotal trial will provide evidence to fulfil a crucial knowledge gap regarding a common and a fundamental intervention in critical care.

Dynamic Inflammatory Changes and Nutritional Risk Scores in ICU Patients Aged 65 Years and Older

"This prospective observational study aims to evaluate the prognostic value of dynamic changes in the serum uric acid-to-albumin ratio (UAR) measured on admission (Day 0) and on Day 3, along with mNUTRIC and PNI scores, regarding 28-day mortality in intensive care patients aged 65 and older."

Cycling Within an Interactive and Immersive Virtual Environment During Critical Illness: a Patient-centred Approach for Lower Limb Rehabilitation

This study aims to investigate whether combining cycling exercise with an immersive and interactive virtual reality (VR) environment improves motivation compared with cycling without visual support or cycling while watching a route on a television screen in critically ill patients admitted to the intensive care unit (ICU). This randomized, within-subject crossover study will include 20 adult ICU patients who have been admitted for at least 7 days, have received mechanical ventilation for at least 48 hours, and are able to perform active cycling exercise. Each participant will complete three 10-minute cycling sessions under different conditions: (1) cycling without visual support (Basic-Cycle), (2) cycling while watching a cycling route on a television screen (TV-Cycle), and (3) cycling within an immersive, interactive VR environment (VR-Cycle). The three conditions will be performed in random order over three consecutive days, with the cycling resistance kept constant across conditions for each participant. The primary outcome is intrinsic motivation, assessed using the Situational Motivation Scale (SIMS). Secondary outcomes include other dimensions of motivation, perceived dyspnea, lower limb fatigue, pain, cycling distance, and safety measures, including vital signs and adverse events. This study will provide insight into the potential of VR-assisted cycling to improve patient motivation and engagement during early rehabilitation in the ICU.

Stress Hyperglycemia Ratio and Glucose Variability in Critically Ill Patients

This prospective cohort study aims to evaluate the stress hyperglycemia ratio and glucose variability among critically ill patients admitted to the intensive care unit.

Alpha 2 Agonists for Sedation to Produce Better Outcomes From Critical Illness (A2B Trial)

Many patients in intensive care (ICU) need help to breathe on a breathing machine and need pain killers and sedatives to keep them comfortable and pain free. However, keeping patients too deeply sedated can make their ICU stay longer, can cause ICU confusion (delirium) and afterwards may cause distressing memories. Ideally patients should be kept less sedated, but it is difficult to get the balance of sedation and comfort right. The investigators want to know whether starting an alpha2-agonist drug early in ICU can help keep patients more lightly sedated but still comfortable, and whether patients spend less time on the ventilator. The investigators also want to know how safe they are and if they can improve important outcomes during ICU stay and during recovery. The investigators also want to know if they are value for money.

Beyond Voluntary Effort: Reliability and Validity of Magnetic Femoral Nerve Stimulation for Assessing Quadriceps Strength in Critically Ill Patient

Intensive care unit-acquired weakness (ICU-AW) is a common complication of critical illness and can negatively affect recovery and long-term physical functioning. Early and reliable assessment of muscle strength is essential for detecting muscle weakness and monitoring changes during an intensive care unit (ICU) stay. However, conventional strength assessments, such as manual muscle testing, require voluntary muscle contractions, making them unsuitable for patients who are not yet cooperative and limiting the possibility of assessing muscle strength during the early stages of critical illness. Magnetic femoral nerve stimulation offers an alternative, non-volitional approach to assessing quadriceps muscle strength. Nevertheless, the reliability and validity of this technique in critically ill patients remain insufficiently established. This prospective methodological study aims to investigate the reliability and convergent validity of quadriceps twitch force measurements obtained using magnetic femoral nerve stimulation in critically ill patients. A total of 33 cooperative adult patients admitted to medical or surgical ICUs will be included. Participants will undergo repeated quadriceps twitch force assessments over two consecutive days, performed by two assessors. Measurements will be conducted using a custom-developed frame designed to facilitate standardized quadriceps strength assessment at the bedside. Both single and paired magnetic stimulation techniques will be evaluated. The primary outcome is the intra-rater reliability of paired twitch force measurements. Secondary outcomes include the inter-rater reliability of paired twitch force measurements, the intra-rater and inter-rater reliability of single twitch force measurements, and the convergent validity of twitch force measurements assessed through their association with maximal voluntary contraction force and potentiated twitch force. Reliability and agreement will be evaluated using intraclass correlation coefficients and complementary measurement error analyses. Establishing these measurement properties could support objective, non-volitional muscle strength assessment in critically ill patients, including those unable to participate in conventional strength testing. This could facilitate early baseline strength assessment, longitudinal monitoring of muscle recovery, and the evaluation of interventions aimed at preventing or treating ICU-AW..

Real-time NOMA Evaluation

Alerts related to outlier clinician behavior are generated in real-time by an intelligent system continuously scraping EHR (electronic health record) data. These alerts are passed to the bedside and their potential impact on bedside clinical behavior is evaluated.

Establishing Normative Data for Pupillometer Assessments in Neuro-Intensive Care

The purpose of this study is to collect a large amount of data that may assist in addressing the gap in knowledge of understanding pupillometer readings using a pupillometer device. The aim of this project is to establish normative values for pupillometer data. Measures of central tendency will be developed for the variables provided by automated pupillary exams, which will provide an enhanced understanding of clinically appropriate pupil values for size, reactivity, and neurological pupil index.

Behavioral Economic & Staffing Strategies in the ICU

The overarching goal of this study is to support the "real world" assessment of strategies used to foster adoption of several highly efficacious evidence-based practices in healthcare systems that provide care to critically ill adults with known health disparities. Investigators will specifically evaluate two discrete strategies grounded in behavioral economic and implementation science theory (i.e., real-time audit and feedback and registered nurse implementation facilitation) to increase adoption of the ABCDEF bundle in critically ill adults.

Physiological Dead Space and Intensive Care Mortality in Mechanically Ventilated Patients

This study investigates the relationship between physiological dead space and clinical outcomes, specifically mortality and discharge status, in adult patients receiving invasive mechanical ventilation in the intensive care unit (ICU). Physiological dead space refers to ventilated but non-perfused regions of the lungs and can be quantified using the Enghoff-modified Bohr equation based on capnographic and arterial CO₂ measurements. While volumetric capnography is a valuable tool in anesthesiology and perioperative care, its use in ICU settings remains limited. By continuously monitoring physiological dead space at the bedside, this study aims to provide real-time insight into ventilation-perfusion mismatch and assess its prognostic significance in critically ill patients.

Post Intensive Care Unit Atrial Fibrillation

Atrial fibrillation (AF) is a common heart rhythm disorder in the intensive care unit (ICU). It can be precipitated by multiple factors but it is unclear whether AF persists after discharge from the ICU, and long term. This study will investigate whether AF recurs up to one year after ICU discharge.

Multidimensional Dysfunction in Patients With Chronic Critical Illness in China

Over the past two decades, rapid advances in critical care medicine have markedly reduced short-term mortality among critically ill patients. As a result, a growing number of patients survive the acute phase of critical illness but do not recover quickly. Instead, they develop chronic critical illness (CCI), which is characterized by prolonged dependence on intensive care, including prolonged mechanical ventilation, persistent organ dysfunction, recurrent infections, and extended intensive care unit (ICU) stay. Patients with CCI have a heavy symptom burden and consume substantial healthcare resources, and many survivors experience persistent physical, cognitive, and psychological impairments after hospital discharge. Although CCI has gained increasing attention in recent years, existing studies still have multiple limitations. The number of patients with CCI in China continues to rise, and critical care delivery models vary widely across regions and healthcare institutions. There is therefore an urgent need for a large-scale multicenter observational study to systematically characterize the epidemiological features, multidimensional functional impairment profiles, and long-term functional outcomes of Chinese patients with CCI. The findings will provide an evidence-based foundation for developing a scientific post-ICU continuum of care for this population.

Factors Influencing Outcomes in ECMO and Impella Patients: Metabolic and Thyroid Hormone Dynamics

This prospective, single-center, consecutive observational study evaluates clinical, metabolic, and endocrine factors influencing survival and clinical outcomes in adult patients undergoing temporary mechanical circulatory support at the Cardiovascular Intensive Care Unit of Gottsegen Gyorgy National Cardiovascular Institute. While traditional cardiovascular risk factors in critically ill patients are well established, non-cardiovascular variables such as endocrine dysfunction, previous functional and nutritional status, metabolic parameters and clinical complications significantly impact short- and long-term outcomes. The study consecutively enrolls all eligible adult patients admitted to the intensive care unit requiring extracorporeal membrane oxygenation (ECMO) or Impella treatment. The primary objective is to evaluate 28-day and ICU mortality, while secondary objectives include characterizing cardiac and non-cardiac complications, nutritional status changes, and hormonal dysregulations.