Patient-Specific Injury Metrics Predict Early Biomarker Response in Multiply Injured Patients

poster abstractIntroduction: It is important to identify multiply injured patients (MIPs) that can tolerate high-magnitude procedures and those at risk for complications. Determining how injury leads to immunologic dysfunction could identify MIPs at risk for complications. We explored a new precision medicine approach in which we determined how patientspecific injury metrics corresponded to changes in cytokines in a prospective cohort of MIPs. Methods: This was a prospective observational cohort of 40 MIPs, 18-55 yo, admitted to surgical ICU having had full axial CTs done at admission. Mechanical tissue damage was quantified by calculating volumetric measures of injuries from CT scans into the Tissue Damage Volume score (TDV). Ischemic tissue damage was calculated by calculation of all abnormal Shock Volumes (SV) (heart rate/systolic blood pressure > 0.9) in the first 24hr after injury. TIMS was calculated by combining mechanical and ischemic tissue damage: TIMS = TDV+5*SV. Linear regression was performed between TIMS and 21 cytokines including interleukin (IL)-6; IL-8; IL-10; IL-1RA; IL-2RA; MCP-1 drawn at 0hr, 8hr, and 24hr after injury. Linear regression was also performed between the cytokines, Injury Severity Score (ISS) and minimum pH (day 1). Results: Mean and median ISS was 29 (range 9 – 66). Minimum pH demonstrated best correspondence to cytokine levels measured 0hr and 8hr after injury. TIMS demonstrated the best correspondence to cytokine levels 24hr after injury. ISS demonstrated minimal predictive value of cytokines at any timepoint. Discussion: A precision medicine approach using a patient-specific quantity of injury predicted trauma-associated changes in circulating cytokines at 0hr, 8 hr, and 24 hr after surgery. This corresponds favorably with timing of orthopaedic surgical decisions regarding staged fracture interventions. While clinical significance of these findings is unknown, computational data analyses of temporal cytokine changes have been shown to be predictive of adverse outcomes after injury

Asymmetrical Body Perception: A Possible Role for Neural Body Representations

Perception of one\u27s body is related not only to the physical appearance of the body, but also to the neural representation of the body. The brain contains many body maps that systematically differ between right- and left-handed people. In general, the cortical representations of the right arm and right hand tend to be of greater area in the left hemisphere than in the right hemisphere for right-handed people, whereas these cortical representations tend to be symmetrical across hemispheres for left-handers. We took advantage of these naturally occurring differences and examined perceived arm length in right- and left-handed people. When looking at each arm and hand individually, right-handed participants perceived their right arms and right hands to be longer than their left arms and left hands, whereas left-handed participants perceived both arms accurately. These experiments reveal a possible relationship between implicit body maps in the brain and conscious perception of the body

THE PATIENT-SPECIFIC INJURY SCORE: PRECISION MEDICINE IN TRAUMA PATIENTS PREDICTS ORGAN DYSFUNCTION AND OUTCOMES

poster abstractIntroduction: Current injury scoring systems in polytraumatized patients are limited at predicting patient outcomes. We present a novel method that quantifies mechanical tissue damage and cumulative hypoperfusion using a precision medicine approach. We hypothesized that a Patient-Specific Injury score formulated from individualized injury indices would stratify patient risk for developing organ dysfunction after injury. We compared correspondence between PSI and the Injury Severity Score with outcomes of organ dysfunction and MOF. Methods: Fifty Multiply-injured-patients (MIPs) were studied. Tissue Damage Volume scores were measured from admission pan-axial CT scans using purpose-designed post-processing software to quantify volumetric magnitude and distribution of injuries. Ischemic injury was quantified using Shock Volumes. SV is a time-magnitude integration of shock index. Values above 0.9 were measured in the 24-hours after injury. Metabolic response was quantified by subtracting the lowest first 24 hr pH from 7.40. PSI combines these indices into the formula: PSI=[0.2TDV+SV]*MR. Correspondence coefficients from regression modeling between PSI and organ dysfunction, measured by the Marshall Multiple Organ Dysfunction score averaged from days 2-5 post-injury, were compared to similar regression models of ISS vs. day 2-5 MOD-scores. We compared PSI and ISS in patients that did or did not develop MOF. Results: PSI demonstrated better correlation to organ dysfunction (r2=0.576) in comparison to ISS (r2=0.393) using the MOD-score on days 2-5. Mean PSI increased 3.4x(58.5vs.17.0;p<0.02) and ISS scores increased 1.4x(39.0vs.28.0;p=0.10) in patients that developed MOF versus those that did not. Conclusions: This study shows that a precision medicine approach that integrates patient-specific indices of mechanical tissue damage, ischemic tissue injury, and metabolic response better corresponds to phenotypic changes including organ dysfunction and MOF compared to ISS in MIPs. The PSI-score can be calculated within 24 hours of injury, making it useful for stratifying risk and predicting the magnitude of organ dysfunction to anticipate

The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture

Contains fulltext : 220729.pdf (publisher's version ) (Open Access)The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light onto multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multicellular tissue architecture. By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, we generate a reconstructed TME that closely resembles tumour growth as observed in human lesions and supports cell survival and function. We demonstrate that the OMC is suitable and outperforms conventional 2D co-cultures for the study of TME-imprinting mechanisms. Within the OMC, we observe the tumour-driven conversion of cDC2s into CD14(+) DCs, characterized by an immunosuppressive phenotype. The OMC provides a valuable approach to study how a TME affects the immune system

Doctor can I buy a new kidney? I've heard it isn't forbidden: what is the role of the nephrologist when dealing with a patient who wants to buy a kidney?

Organ trafficking is officially banned in several countries and by the main Nephrology Societies. However, this practice is widespread and is allowed or tolerated in many countries, hence, in the absence of a universal law, the caregiver may be asked for advice, placing him/her in a difficult balance between legal aspects, moral principles and ethical judgments. In spite of the Istanbul declaration, which is a widely shared position statement against organ trafficking, the controversy on mercenary organ donation is still open and some experts argue against taking a negative stance. In the absence of clear evidence showing the clinical disadvantages of mercenary transplantation compared to chronic dialysis, self-determination of the patient (and, with several caveats, of the donor) may conflict with other ethical principles, first of all non-maleficence. The present paper was drawn up with the participation of the students, as part of the ethics course at our medical school. It discusses the situation in which the physician acts as a counselor for the patient in the way of a sort of “reverse” informed consent, in which the patient asks advice regarding a complex personal decision, and includes a peculiar application of the four principles (beneficence, non-maleficence, justice and autonomy) to the donor and recipient parties

Putting to a bigger hole:golf performance relates to perceived size

When people are engaged in a skilled behavior, such as occurs in sports, their perceptions relate optical information to their performance. In the present research, we demonstrate the effects of performance on size perception in golfers. We found that golfers who played better judged the hole to be bigger than did golfers who did not play as well. In follow-up laboratory experiments, participants putted on a golf mat from a location near or far from the hole and then judged the size of the hole. Participants who putted from the near location perceived the hole to be bigger than did participants who putted from the far location. Our results demonstrate that perception is influenced by the perceiver's current ability to act effectively in the environment

The Effects of Handedness and Reachability on Perceived Distance

Previous research has suggested that perceived distances are scaled by the action capabilities of the body. The present studies showed that when "reachability" is constrained due to a difficult grasp required to pick up an object, perceived distance to the object increases. Participants estimated the distances to tools with handle orientations that made them either easy or difficult to grasp with their dominant and nondominant hands. Right-handed participants perceived tools that were more difficult to grasp to be farther away than tools that were easier to grasp. However, perceived distance did not differ in left-handed participants. These studies suggest that, when reaching toward a target, the distance to that target is scaled in terms of how far one can effectively reach, given the type of reaching posture that is executed. Furthermore, this effect is modulated by handedness

The long road of pain: chronic pain increases perceived distance

Spatial perception is sensitive to the energetic costs required to perform intended actions. For example, hills look steeper to people who are fatigued or burdened by a heavy load. Similarly, perceived distance is also influenced by the energy required to walk or throw to a target. Such experiments demonstrate that perception is a function, not just of optical information, but also of the perceiver's potential to act and the energetic costs associated with the intended action. In the current paper, we expand on the notion of "cost" by examining perceived distance in patients diagnosed with chronic pain, a multifactorial disease, which is experienced while walking. We found that chronic pain patients perceive target distances to be farther away compared with a control group. These results indicate the physical, and perhaps emotional, costs of chronic pain affect spatial perceptions