From ICU Syndromes to ICU Subphenotypes: Consensus Report and Recommendations for Developing Precision Medicine in the ICU.

Critical care uses syndromic definitions to describe patient groups for clinical practice and research. There is growing recognition that a "precision medicine" approach is required and that integrated biologic and physiologic data identify reproducible subpopulations that may respond differently to treatment. This article reviews the current state of the field and considers how to successfully transition to a precision medicine approach.

Corticosteroids for infectious critical illness: A multicenter target trial emulation stratified by predicted organ dysfunction trajectory.

Corticosteroids decrease the duration of organ dysfunction in a range of infectious critical illnesses, but their risk and benefit are not fully defined using this construct. This retrospective multicenter study aimed to evaluate the association between usage of corticosteroids and mortality of patients with infectious critical illness by emulating a target trial framework. The study employed a novel stratification method with predictive machine learning (ML) subphenotyping based on organ dysfunction trajectory.

Low-dose carbon monoxide suppresses metastatic progression of disseminated cancer cells.

Low-dose carbon monoxide (CO) is under investigation in clinical trials to treat non-cancerous diseases and has an excellent safety profile. Due to early detection and cancer awareness, an increasing number of cancer patients are diagnosed at early stages, when potentially curative surgical resection can be done. However, many patients ultimately experience recurrence.

Sepsis subphenotyping based on organ dysfunction trajectory.

Background: Sepsis is a heterogeneous syndrome, and the identification of clinical subphenotypes is essential. Although organ dysfunction is a defining element of sepsis, subphenotypes of differential trajectory are not well studied. We sought to identify distinct Sequential Organ Failure Assessment (SOFA) score trajectory-based subphenotypes in sepsis.

Conditional deletion of myeloid-specific mitofusin 2 but not mitofusin 1 promotes kidney fibrosis.

Macrophages exert critical functions during kidney injury, inflammation, and tissue repair or fibrosis. Mitochondrial structural and functional aberrations due to an imbalance in mitochondrial fusion/fission processes are implicated in the pathogenesis of chronic kidney disease. Therefore, we investigated macrophage-specific functions of mitochondrial fusion proteins, mitofusin (MFN)1 and MFN2, in modulating macrophage mitochondrial dynamics, biogenesis, oxidative stress, polarization, and fibrotic response.

Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19.

COVID-19-associated respiratory failure offers the unprecedented opportunity to evaluate the differential host response to a uniform pathogenic insult. Understanding whether there are distinct subphenotypes of severe COVID-19 may offer insight into its pathophysiology. Sequential Organ Failure Assessment (SOFA) score is an objective and comprehensive measurement that measures dysfunction severity of six organ systems, i.

How Does Contact Length Impact Titanium Tapered Splined Stem Stability: A Biomechanical Matched Pair Cadaveric Study.

Background: Titanium tapered stems (TTS) achieve fixation in the femoral diaphysis and are commonly used in revision total hip arthroplasty. The initial stability of a TTS is critical, but the minimum contact length needed and impact of implant-specific taper angles on axial stability are unknown. This biomechanical study was performed to better guide operative decision-making by addressing these clinical questions.

Early Aseptic Loosening with Increased Presence and Severity of Backside Burnishing in the Optetrak Logic Posterior-Stabilized Total Knee Arthroplasty Femoral Component.

Concerns persist that the Optetrak Logic posterior-stabilized (PS) total knee arthroplasty (TKA) femoral component might correlate with early failures due to aseptic loosening. The primary aim of this study was to examine if the use of the Optetrak Logic PS femoral component is associated with early (<5 years) and more extensive aseptic loosening compared with other PS femoral components. This is a single-institution retrieval analysis and revision registry study (based on prospectively collected data) of 27 failed primary PS TKA patients with loose femoral components that underwent revision TKAs between 2016 and 2019.

Attributable mortality of acute respiratory distress syndrome: a systematic review, meta-analysis and survival analysis using targeted minimum loss-based estimation.

Background: Although acute respiratory distress syndrome (ARDS) is associated with high mortality, its direct causal link with death is unclear. Clarifying this link is important to justify costly research on prevention of ARDS.

Objective: To estimate the attributable mortality, if any, of ARDS.

A Comparative Analysis of the Respiratory Subscore of the Sequential Organ Failure Assessment Scoring System.

The Sequential Organ Failure Assessment (SOFA) tool is a commonly used measure of illness severity. Calculation of the respiratory subscore of SOFA is frequently limited by missing arterial oxygen pressure (Pa) data. Although missing Pa data are commonly replaced with normal values, the performance of different methods of substituting Pa for SOFA calculation is unclear.

Rapid Transition of a PICU Space and Staff to Adult Coronavirus Disease 2019 ICU Care.

Objectives: We describe the process by which a PICU and a PICU care team were incorporated into a hospital-wide ICU care model during the coronavirus disease 2019 pandemic.

Design: A descriptive, retrospective report from a single-center PICU.

Setting: Twenty-three bed, quaternary PICU, within an 862-bed hospital.

Patient Rights at the End of Life: The Ethics of Aid-in-Dying.

Purpose/objectives: The end-of-life needs and desires of patients, whether it is related to a terminal illness or age-related end-of-life physiological function, can vary from patient to patient. Each dying patient's case should be approached in an individual and patient-centered fashion while supporting the dying patient's desired preferences related to end-of-life treatment. This serves to recognize the dying patient's individual rights related to self-determination of preserving his or her dignity during the end-of-life process.

No Difference in Force Required for Intraprosthetic Dislocation of Mixed Manufacturer vs Same Manufacturer Dual Mobility Articulations.

Background: To avoid the morbidity of removing well-fixed implants during revision surgery, the off-label practice of mixing femoral heads with dual mobility (DM) polyethylene liners from different manufacturers is commonly performed. The resistance to intraprosthetic dislocation, when the inner prosthetic head disengages from the polyethylene bearing, between mixed and same manufacturer constructs remains unknown.

Methods: Between January 2010 and July 2018, 168 DM liners were retrieved.

Mitophagy-dependent macrophage reprogramming protects against kidney fibrosis.

Mitophagy, by maintaining mitochondrial quality control, plays a key role in maintaining kidney function and is impaired in pathologic states. Macrophages are well known for their pathogenic role in kidney fibrosis. Here, we report that PINK1/Parkin-mediated mitophagy in macrophages is compromised in experimental and human kidney fibrosis.

Fatty acid synthase downregulation contributes to acute lung injury in murine diet-induced obesity.

The prevalence of obesity is rising worldwide and obese patients comprise a specific population in the intensive care unit. Acute respiratory distress syndrome (ARDS) incidence is increased in obese patients. Exposure of rodents to hyperoxia mimics many of the features of ARDS.

Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials.

Background: Observational studies suggest that some patients meeting criteria for ARDS no longer fulfill the oxygenation criterion early in the course of their illness. This subphenotype of rapidly improving ARDS has not been well characterized. We attempted to assess the prevalence, characteristics, and outcomes of rapidly improving ARDS and to identify which variables are useful to predict it.

Hip Fracture in the Frail Elderly: Making the Case for Early Integration of Palliative Care and Timely Hospice Referral.

With the projected increase of an aging population in the upcoming decades, coupled with increasing elderly longevity, the incidence of hip fractures among this vulnerable population is expected to grow. Current evidence reveals high mortality rates within 6 months to 1 year among frail elderly patients who suffer hip fracture. In addition, the presence of multiple chronic conditions negatively impacts mortality rates in this vulnerable population.

Developing interprofessional health competencies in a virtual world.

Background: Virtual worlds provide a promising means of delivering simulations for developing interprofessional health skills. However, developing and implementing a virtual world simulation is a challenging process, in part because of the novelty of virtual worlds as a simulation platform and also because of the degree of collaboration required among technical and subject experts. Thus, it can be difficult to ensure that the simulation is both technically satisfactory and educationally appropriate.