Complement C3 serum levels in anorexia nervosa: a potential biomarker for the severity of disease?

BackgroundAnorexia nervosa carries the highest mortality rate of any psychiatric disorder. Even the most critically ill anorexic patients may present with normal 'standard' laboratory values, underscoring the need for a new sensitive biomarker. The complement cascade, a major component of innate immunity, represents a driving force in the pathophysiology of multiple inflammatory disorders. The role of complement in anorexia nervosa remains poorly understood. The present study was designed to evaluate the role of complement C3 levels, the extent of complement activation and of complement hemolytic activity in serum, as potential new biomarkers for the severity of anorexia nervosa.Patients and methodsThis was a prospective cohort study on 14 patients with severe anorexia nervosa, as defined by a body mass index (BMI) <14 kg/m2. Serum samples were obtained in a biweekly manner until hospital discharge. A total of 17 healthy subjects with normal BMI values served as controls. The serum levels of complement C3, C3a, C5a, sC5b-9, and of the 50% hemolytic complement activity (CH50) were quantified and correlated with the BMIs of patients and control subjects.ResultsSerum C3 levels were significantly lower in patients with anorexia nervosa than in controls (median 3.7 (interquartile range (IQR) 2.5-4.9) vs 11.4 (IQR 8.9-13.7, P <0.001). In contrast, complement activation fragments and CH50 levels were not significantly different between the two groups. There was a strong correlation between index C3 levels and BMI (Spearman correlation coefficient = 0.71, P <0.001).ConclusionsComplement C3 serum levels may represent a sensitive new biomarker for monitoring the severity of disease in anorexia nervosa. The finding from this preliminary pilot study will require further investigation in future prospective large-scale multicenter trials

Bias towards publishing positive results in orthopedic and general surgery: a patient safety issue?

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"Metabolic staging" after major trauma - a guide for clinical decision making?

Metabolic changes after major trauma have a complex underlying pathophysiology. The early posttraumatic stress response is associated with a state of hyperinflammation, with increased oxygen consumption and energy expenditure. This hypercatabolic state must be recognized early and mandates an early nutritional management strategy. A proactive concept of early enteral "immunonutrition" in severely injured patients, is aimed at counterbalancing the negative aspects of hyperinflammation and hypercatabolism in order to reduce the risk of late complications, including infections and posttraumatic organ failure. Recently, the concept of "metabolic staging" has been advocated, which takes into account the distinct inflammatory phases and metabolic phenotypes after major trauma, including the "ischemia/reperfusion phenotype", the "leukocytic phenotype", and the "angiogenic phenotype". The potential clinical impact of metabolic staging, and of an appropriately adapted "metabolic control" and nutritional support, remains to be determined

Introducing standardized “readbacks” to improve patient safety in surgery: a prospective survey in 92 providers at a public safety-net hospital

Background: Communication breakdowns represent the main root cause of preventable complications which lead to harm to surgical patients. Standardized readbacks have been successfully implemented as a main pillar of professional aviation safety for decades, to ensure a safe closed-loop communication between air traffic control and individual pilots. The present study was designed to determine the perception of staff in perioperative services regarding the role of standardized readbacks for improving patient safety in surgery at a single public safety-net hospital and level 1 trauma center. Methods: A 12-item questionnaire was sent to 180 providers in perioperative services at Denver Health Medical Center. The survey was designed to determine the individual participants’ perception of (1) appropriateness of current readback processes; (2) willingness to attend a future training module on this topic; (3) specific scenarios in which readbacks may be effective; and (4) perceived major barriers to the implementation of standardized readbacks. Survey results were compared between departments (surgery versus anesthesia) and between specific staff roles (attending or midlevel provider, resident physician, nursing staff), using non-parametric tests. Results: The response rate to the survey was 50.1 % (n = 92). Respondents overwhelmingly recognized the role of readbacks in reducing communication errors and improving patient safety. There was a strong agreement among respondents to support participation in a readbacks training program. There was no difference in the responses between the surgery and anesthesia departments. There was a statistically significant difference in the healthcare providers willingness to attend a short training module on readbacks (p < 0.001). Resident physicians were less likely to endorse the importance of readbacks in reducing communication errors (p = 0.01) and less willing to attend a short training module on readbacks (p < 0.001), as compared to staff providers and nursing staff. The main challenge for respondents, which emanated from their responses, appeared to relate to determining the ideal scenarios in which readbacks may be most appropriately used. Overall, respondents strongly felt that readbacks had an important role in patient handoffs, patient orders regarding critical results, counting and verifying surgical instruments, and delegating multiple perioperative tasks. Conclusion: The majority of all respondents appear to perceive standardized readbacks as an effective tool for reducing and/or preventing adverse events in the care of surgical patients, derived from a breakdown in communication among perioperative caregivers. Further work needs to be done to define the exact clinical scenarios in which readbacks may be most efficiently implemented, including the definition of a uniform set of scripted quotes and phrases, which should likely be standardized in concert with the aviation safety model

Peroxisome Proliferator-Activated Receptors: “Key” Regulators of Neuroinflammation after Traumatic Brain Injury

Traumatic brain injury is characterized by neuroinflammatory pathological sequelae which contribute to brain edema and delayed neuronal cell death. Until present, no specific pharmacological compound has been found, which attenuates these pathophysiological events and improves the outcome after head injury. Recent experimental studies suggest that targeting peroxisome proliferator-activated receptors (PPARs) may represent a new anti-inflammatory therapeutic concept for traumatic brain injury. PPARs are “key” transcription factors which inhibit NFκB activity and downstream transcription products, such as proinflammatory and proapoptotic cytokines. The present review outlines our current understanding of PPAR-mediated neuroprotective mechanisms in the injured brain and discusses potential future anti-inflammatory strategies for head-injured patients, with an emphasis on the putative beneficial combination therapy of synthetic cannabinoids (e.g., dexanabinol) with PPARα agonists (e.g., fenofibrate)

Vascular injuries after minor blunt upper extremity trauma: pitfalls in the recognition and diagnosis of potential "near miss" injuries

<p>Abstract</p> <p>Background</p> <p>Low energy trauma to the upper extremity is rarely associated with a significant vascular injury. Due to the low incidence, a high level of suspicion combined with appropriate diagnostic algorithms are mandatory for early recognition and timely management of these potentially detrimental injuries.</p> <p>Methods</p> <p>Review of the pertinent literature, supported by the presentation of two representative "near miss" case examples.</p> <p>Results</p> <p>A major diagnostic pitfall is represented by the insidious presentation of significant upper extremity arterial injuries with intact pulses and normal capillary refill distal to the injury site, due to collateral perfusion. Thus, severe vascular injuries may easily be missed or neglected at the upper extremity, leading to a long-term adverse outcome with the potential need for a surgical amputation.</p> <p>Conclusion</p> <p>The present review article provides an outline of the diagnostic challenges related to these rare vascular injuries and emphasizes the necessity for a high level of suspicion, even in the absence of a significant penetrating or high-velocity trauma mechanism.</p

Pathophysiology of septic encephalopathy - an unsolved puzzle

The exact cellular and molecular mechanisms of sepsis-induced encephalopathy remain elusive. The breakdown of the blood-brain barrier (BBB) is considered a focal point in the development of sepsis-induced brain damage. Contributing factors for the compromise of the BBB include cytokines and chemokines, activation of the complement cascade, phagocyte-derived toxic mediators, and bacterial products. To date, we are far from fully understanding the neuropathology that develops as a secondary remote organ injury as a consequence of sepsis. However, recent studies suggest that bacterial proteins may readily cross the functional BBB and trigger an inflammatory response in the subarachnoid space, in absence of a bacterial invasion. A better understanding of the pathophysiological events leading to septic encephalopathy appears crucial to advance the clinical care for this vulnerable patient population