Kyros Ipaktchi

Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis.

IntroductionSeptic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction during experimental sepsis.MethodsUsing the standardised caecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with either neutralising anti-C5a antibody or pre-immune immunoglobulin (Ig) G as a placebo. Sham-operated animals served as internal controls.ResultsPlacebo-treated septic rats showed severe BBB dysfunction within 24 hours, accompanied by a significant upregulation of pituitary C5a receptor and pro-inflammatory cytokine expression, although gene levels of growth hormone were significantly attenuated. The pathophysiological changes in placebo-treated septic rats were restored by administration of neutralising anti-C5a antibody to the normal levels of BBB and pituitary function seen in the sham-operated group.ConclusionsCollectively, the neutralisation of C5a greatly ameliorated pathophysiological changes associated with septic encephalopathy, implying a further rationale for the concept of pharmacological C5a inhibition in sepsis.

Burn-induced organ dysfunction: Vagus nerve stimulation attenuates organ and serum cytokine levels

INTRODUCTIONnThe interaction of the CNS and the immune system is well known. A parasympathetic anti-inflammatory pathway has recently been described. Both electrical and pharmacological parasympathetic stimulation attenuate proinflammatory mediator generation. Burn induces abacterial cytokine generation and we sought to evaluate whether parasympathetic stimulation after experimental burn decreases cardiodepressive mediator generation.nnnMATERIAL AND METHODSnA 30% TBSA full-thickness rat burn model was used. After microsurgical preparation of the cervical portion of the vagus nerve, we performed electric vagus nerve stimulation. Serum was harvested and organ samples of heart and liver were homogenized. Samples were subjected to sandwich-ELISA specific for TNF-alpha, IL-1beta and IL-6. Heart rate measurements were done using left ventricular microcatheterization. Statistical analysis was done using Students t-tests and analysis of variance (ANOVA).nnnRESULTSnBurn induced a significant rise of TNF-alpha, IL-1beta and IL-6 in organ homogenates and serum. After cervical vagal electrostimulation, serum and organ homogenate levels of proinflammatory cytokines were markedly reduced compared to burn controls. Left ventricular microcatheter assessment demonstrated no cardiodepressive effect of the vagal stimulation itself.nnnCONCLUSIONnOur results encourage further research regarding the neuroimmunologic background of burn, possibly leading to the development of a novel therapeutic approach to burn-induced organ dysfunction and immunodysregulation.

Bench-to-bedside review: Burn-induced cerebral inflammation--a neglected entity?

Severe burn injury remains a major burden on patients and healthcare systems. Following severe burns, the injured tissues mount a local inflammatory response aiming to restore homeostasis. With excessive burn load, the immune response becomes disproportionate and patients may develop an overshooting systemic inflammatory response, compromising multiple physiological barriers in the lung, kidney, liver, and brain. If the blood–brain barrier is breached, systemic inflammatory molecules and phagocytes readily enter the brain and activate sessile cells of the central nervous system. Copious amounts of reactive oxygen species, reactive nitrogen species, proteases, cytokines/chemokines, and complement proteins are being released by these inflammatory cells, resulting in additional neuronal damage and life-threatening cerebral edema. Despite the correlation between cerebral complications in severe burn victims with mortality, burn-induced neuroinflammation continues to fly under the radar as an underestimated entity in the critically ill burn patient. In this paper, we illustrate the molecular events leading to blood–brain barrier breakdown, with a focus on the subsequent neuroinflammatory changes leading to cerebral edema in patients with severe burns.

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

BackgroundLow 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.MethodsReview of the pertinent literature, supported by the presentation of two representative near miss case examples.ResultsA 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.ConclusionThe 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.

The role of bone allografts in the treatment of angular malunions of the distal radius.

PURPOSEnTwo cohorts of patients who had corrective osteotomies and volar platings for malunited fractures of the distal radius were compared retrospectively to determine whether the time to union and the outcome were affected by bone allograft.nnnMETHODSnPatients in the first group (n = 14) did not receive any bone graft; patients in the second group (n = 14) had allograft bone chips following volar plating. Indications for surgery, surgical technique, and postoperative rehabilitation were the same in both groups. Volar cortical contact was maintained using a volar locking plate in all patients. Radiographic parameters of deformity correction, time to union, wrist and forearm range of motion, grip strength, patient-rated wrist evaluation and Disabilities of the Arm, Shoulder, and Hand questionnaire were used to evaluate the outcome before and after the surgery. Average follow-up time was 36 weeks. Patients who had diabetes, who smoked, who had a body mass index of more than 35, and who required lengthening for deformity correction were excluded from the study.nnnRESULTSnOsteotomies in both groups healed without loss of surgical correction. Final outcome and time to union revealed no significant differences, clinically or statistically, between the 2 groups. The Disabilities of the Arm, Shoulder, and Hand score was improved in both groups.nnnCONCLUSIONSnWhen volar cortical contact was maintained using a volar locked plate, bone allograft at the osteotomy site did not improve the final outcome.nnnTYPE OF STUDY/LEVEL OF EVIDENCEnTherapeutic III.

Disturbances of the hypothalamic-pituitary-adrenal axis and plasma electrolytes during experimental sepsis.

BackgroundSepsis continues to be a poorly understood syndrome with a high mortality rate. While we are beginning to decipher the intricate interplay of the inflammatory response during sepsis, the precise regulation of the hypothalamic-pituitary-adrenal (HPA) axis and its impact on electrolyte homeostasis during sepsis remains incompletely understood.MethodsSepsis was induced in adult male Sprague-Dawley rats by cecal ligation and puncture (CLP). Plasma samples were obtained as a function of time (6-48 hrs) after CLP and compared with healthy animals (neg ctrl). Samples were analyzed for adrenocorticotropin (ACTH), corticosterone, and aldosterone levels, as well as concentrations of sodium (Na+), potassium (K+), chloride (Cl-), and magnesium (Mg2+).ResultsACTH levels were found to be significantly reduced 6-24 hrs after CLP in comparison to baseline levels and displayed gradual recovery during the later course (24-48 hrs) of sepsis. Plasma corticosterone concentrations exhibited a bell-shaped response, peaking between 6 and 12 hrs followed by rapid decline and concentrations below negative control levels 48 hrs after injury. Aldosterone levels in septic animals were continuously elevated between 6 and 48 hrs. Whereas plasma Na+ levels were found to be persistently elevated following CLP, levels of K+, Cl- and Mg2+ were significantly reduced as a function of time and gradually recovered during the later course of sepsis.ConclusionsCLP-induced sepsis resulted in dynamic changes of ACTH, corticosterone, and aldosterone levels. In addition, electrolyte levels showed significant disturbances after CLP. These electrolyte perturbations might be evoked by a downstream effect or a dysfunctional HPA-axis response during sepsis and contribute to severe complications during sepsis.

Current Treatment Concepts for "Terrible Triad" Injuries of the Elbow

Elbow fracture-dislocations destabilize the elbow, preventing functional rehabilitation. If left untreated, they commonly result in functional compromise and poor outcomes. The terrible triad injury is classically described as a combination of a coronoid process and radial head fractures, as well as a posterolateral elbow dislocation. Surgical treatment to restore stable elbow range of motion has evolved in the past few decades based on increased understanding of elbow biomechanics and the anatomy of these injuries. This article highlights current concepts in the treatment of these complicated injuries.

Adherence to therapy after flexor tendon surgery at a level 1 trauma center

BackgroundNonadherence to postoperative therapy protocols can adversely affect the outcome after flexor tendon surgery. In this study, we hypothesize that patients with partial or no insurance coverage for their aftercare are less likely to attend postoperative therapy sessions and have a higher incidence of a poorer outcome than those who have full insurance coverage.MethodsWe analyzed 159 patients with flexor tendon injuries at a level 1 trauma center. Demographic variables along with the clinical outcome data were collected and cross-tabulated. Associations among descriptive and clinical variables were assessed using Fisher’s Exact tests and chi-square analyses. Comparisons for continuous variables were performed using the Kruskal-Wallis Test.ResultsEighteen patients (11.3xa0%) had an injury in zone 1, followed by 68 (42.8xa0%) in zone 2, 15 (9.4xa0%) in zone 3, 9 (5.7xa0%) in zone 4, 38 (23.9xa0%) in zone 5, and 11 (6.9xa0%) in zone 6. Patients completed 8.2 therapy sessions on average. Patients had state assistance program (40.3xa0%), private insurance (35.2xa0%), Medicaid/Medicare (11.3xa0%), worker’s compensation (8.8xa0%) insurance, or paid themselves (13.2xa0%). Fifty-three (33.3xa0%) patients had excellent outcomes, 46 (29xa0%) had good, 40 (25xa0%) had fair, and 20 (12.5xa0%) had a poor outcome. Patients responsible to pay for their aftercare were significantly less likely to be adherent to therapy and had poorer outcomes than those with full coverage.ConclusionPatients responsible for the pay of their postoperative rehabilitation are less likely to participate in therapy and may be at a higher risk of having a poor outcome.

Assessment of microcirculatory influence on cellular morphology in human burn wound healing using reflectance-mode-confocal microscopy

Previous studies have assessed the effects of changes in microcirculation on wound healing; however, the influence of microcirculation on tissue histomorphology remains widely unknown. Reflectance‐mode‐confocal microscopy (RMCM) enables in vivo tissue observation on a cellular level. We present RMCM data evaluating the local microcirculation and assess the influence on histomorphology during burn healing. RMCM was performed in 12 patients (aged; 36.2±14.2 years, maximum‐burn‐extent: 4% total body surface area) at times 12, 36, and 72 hours after a superficial burn. The following parameters were assessed: quantitative blood‐cell‐flow (cbf), epidermal thickness (Emin), basal‐layer thickness (tbl), and granular cell‐size (Agran). Cbf was found to be 54±3.6u2003cells/minutes (control), increased to 91±3.6u2003cells/minutes (p<0.05) 12 hours postburn; decreased to 71±6.1u2003cells/minutes (p<0.05) (36 hours), and to 63±2.3u2003cells/minutes (p>0.05) 72 hours postburn. Emin was 43.74±3.87u2003μm (control), increased to 51.67±4.04u2003μm (p<0.05) 12 hours, decreased to 48.67±3.51u2003μm (p<0.05) 36 hours, and to 45.33±3.21u2003μm (p>0.05) at 72 hours postburn. Tbl was 14.17±0.6u2003μm (control), increased to 16.93±1.15u2003μm (p<0.05) 12 hours, decreased to 15.93±1.20u2003μm (p<0.05) 32 hours, and to 15.00±0.85u2003μm (p>0.05) 72 hours postburn. Agran was 718±56.20u2003μm2 (control), increased to 901±66.02u2003μm2 (p<0.05) 12 hours, decreased to 826±56.86u2003μm2 36 hours, and 766±65.06u2003μm2 at 72 hours postburn. RMCM enables in vivo observation of wound microcirculation and allows direct assessment of vascular effects on cutaneous histomorphology during the healing course of superficial burns.

Unrecognized hand ischemia after intraarterial drug injection: successful management of a "near miss" event

BackgroundComplications arising from accidental intraarterial drug injections have been described in the past. However, given the multitude of injected substances and complex pathophysiology, guidelines regarding diagnosis and management of patients with intraarterial injections remain vague. As such it remains unclear, when to expect limb ischemia and whether and for how long to monitor patients after intraarterial injections.Case reportWe present the case of a near miss event in an i.v. drug abuser presenting to the emergency department 3 hours after injection of water dissolved zolpidem (Ambien™) tablets into the right ulnar artery. Chief complaint was forearm pain. Clinical examination at the time revealed no concern for limb ischemia and patient was discharged. The patient returned unplanned 18 hours after injection with an ischemic right hand. Angiography revealed no flow in the distal ulnar artery and minimal flow in the palmar arch. Emergent intraarterial thrombolysis with Urokinase was performed and restored hand perfusion. Clinical follow-up 3 months after injury showed full recovery with regular recapillarisation and normal Allen test.ConclusionThis case report highlights the need to rigorously monitor patients with suspected intraarterial injections for potential delayed onset of limb ischemia. This is to our knowledge the first described case report of a successful revascularization after prolonged ischemia with delayed onset after zolpidem injection. We recommend close monitoring of these patients for at least 24 hours in addition to starting prophylactic anticoagulation.