A Comparison Between Pulse Pressure Variation and Right End Diastolic Volume Index as Guides to Resuscitation in a Model of Hemorrhagic Shock in Pigs

Background: Different hemodynamic parameters including static indicators of cardiac preload as right ventricular end-diastolic volume index (RVEDVI) and dynamic parameters as pulse pressure variation (PPV) have been used in the decision-making process regarding volume expansion in critically ill patients. The objective of this study was to compare fluid resuscitation guided by either PPV or RVEDVI after experimentally induced hemorrhagic shock. Methods: Twenty-six anesthetized and mechanically ventilated pigs were allocated into control (group I), PPV (group II), or RVEDVI (group III) group. Hemorrhagic shock was induced by blood withdrawal to target mean arterial pressure of 40 mm Hg, maintained for 60 minutes. Parameters were measured at baseline, time of shock, 60 minutes after shock, immediately after resuscitation with hydroxyethyl starch 6% (130/0.4), 1 hour and 2 hours thereafter. The endpoint of fluid resuscitation was determined as the baseline values of PPV and RVEDVI. Statistical analysis of data was based on analysis of variance for repeated measures followed by the Bonferroni test (p < 0.05). Results: Volume and time to resuscitation were higher in group III than in group II (group III = 1,305 +/- 331 mL and group II = 965 +/- 245 mL, p < 0.05; and group III = 24.8 +/- 4.7 minutes and group II = 8.8 +/- 1.3 minutes, p < 0.05, respectively). All static and dynamic parameters and biomarkers of tissue oxygenation were affected by hemorrhagic shock and nearly all parameters were restored after resuscitation in both groups. Conclusion: In the proposed model of hemorrhagic shock, resuscitation to the established endpoints was achieved within a smaller amount of time and with less volume when guided by PPV than when guided by pulmonary artery catheter-derived RVEDVI.

Standard Examination System for Laparoscopy in Penetrating Abdominal Trauma

Background: The high missed occult small bowel injuries (SBI) associated with laparoscopy in trauma (LIT) is a major reason why some surgeons still preclude LIT today. No standardized laparoscopic examination for evaluation of the peritoneal cavity is described for trauma. The objective of this article is to verify if a systematic standardized laparoscopic approach could correctly identify SBI in the peritoneal cavity for penetrating abdominal trauma (PAT). Methods: Victims with PAT were evaluated in a prospective, nonrandomized study. A total of 75 hemodynamically stable patients with suspected abdominal injuries were operated by LIT and converted to laparotomy if criteria were met: SBI and lesions to blind spot zones-retroperitoneal hematoma, injuries to segments VI or VII of the liver, or injuries to the posterior area of the spleen. Inclusion criteria were equivocal evidence of abdominal injuries or peritonea] penetration; systolic blood pressure >90 mm Hg and <3 L of IV fluids in the first hour of admission; Glasgow Coma Scale score >12; and age >12 years. Exclusion criteria were back injuries; pregnancy; previous laparotomy; and chronic cardiorespiratory disease. Results: Sixty patients were males and there were 38 stab wounds and 37 gunshot wounds. No SBI was missed, but a pancreatic lesion was undiagnosed due to a retroperitoneal hematoma. Twenty patients (26.6%) were converted. Unnecessary laparotomies were avoided in 73.33%. Therapeutic LIT was possible in 22.7%. Accuracy was 98.66% with 97.61% sensitivity and 100% specificity. Conclusions: Standard systematic laparoscopic exploration was 100% effective to detect SBI in the peritoneal cavity. Conversion from LIT to laparotomy should be done if injuries to blind spot zones are found which are poorly evaluated by LIT. Therapeutic LIT is feasible in PAT.

Low Hematocrit Levels Increase Intracranial Pressure in an Animal Model of Cryogenic Brain Injury

Background: Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over optimal fluid management for these patients. This study aimed to investigate the effects of acute hemodilution with hydroxyethyl starch (HES) or lactated Ringer`s solution (LR) in intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in dogs submitted to a cryogenic brain injury model. Methods: Design-Prospective laboratory animal study. Setting-Research laboratory in a teaching hospital. Subjects-Thirty-five male mongrel dogs. Interventions-Animals were enrolled to five groups: control, hemodilution with LR or HES 6% to an hematocrit target of 27% or 35%. Results: ICP and CPP levels were measured after cryogenic brain injury. Hemodilution promotes an increment of ICP levels, which decreases CPP when hematocrit target was estimated in 27.% after hemodilution. However, no differences were observed regarding crystalloid or colloid solution used for hemodilution in ICP and CPP levels. Conclusions: Hemodilution to a low hematocrit level increases ICP and decreases CPP scores in dogs submitted to a cryogenic brain injury. These results suggest that excessive hemodilution to a hematocrit below 30% should be avoided in traumatic brain injury patients.

Preferential use of nonreversed vein grafts in above-knee femoropopliteal bypasses for critical ischemia: Midterm outcome

We evaluated nonreversed vein grafts in above-knee bypasses for chronic critical limb ischemia in a retrospective study with intention-to-treat analysis in patients who underwent above-knee bypass grafting. During a 4-year period, 51 patients (men, 32; women, 19; mean age 66 years) with 53 critically ischemic lower extremities underwent above-knee femoropopliteal bypass grafting. The follow-up evaluation consisted of clinical examination, assessment of the ankle- brachial systolic blood pressure index, and, whenever necessary, duplex scanning. Three ( 5.7%) deaths occurred within 30 days, two from myocardial infarction and one from an undetermined cause. The 2-year cumulative success rate was 82.5 +/- 9.6% for primary patency, 84.6 +/- 8.9% for secondary patency, 90.1 +/- 7.3% for tertiary patency, 86.9 +/- 7.6% for limb salvage, 77.7 +/- 8.4% for survival, 68.0 +/- 11.1% for composite patency, and 68.4 +/- 9.3% for amputation- free survival; the corresponding estimates for vein grafts alone were 86.6 +/- 9.2%, 88.9 +/- 8.6%, 89.0 +/- 8.5%, 88.1 +/- 8.1%, 81.1 +/- 9.1, 76.8 +/- 11.1%, and 72.6 +/- 10.2%. Three prosthetic grafts failed and were replaced with an arm vein graft. Nonreversed vein bypass grafts in above- knee revascularization of critically ischemic limbs are justified.

Neutrophils recruitment during sepsis: Critical points and crossroads

The mechanisms that initiate an inflammatory systemic response to a bacterial infection lead to a high mortality and constitute the first cause of death in Critical Care Units (ICU`s). Sepsis is a poorly understood disease and despite life support techniques and the administration of antibiotics, not much more can be done to improve its diagnosis and treatment. The present article has as main objective to discuss the role of neutrophils recruitment in sepsis, dissecting the molecular mechanisms implicated in this complex process and its importance to the pathogenesis of this outstanding cause of death.

Effects of Fluid Resuscitation on Cardiovascular Performance After Posttraumatic Pneumonectomy

Background: Several factors have been implicated in the high-mortality rate of posttraumatic pneumonectomy. In this study, we evaluated the hemodynamic and echocardiographic changes induced by pneumonectomy and fluid resuscitation after hemorrhagic shock. Methods: Fourteen dogs were bled to a target mean arterial pressure of 40 mmHg. The animals were assigned to two groups: control (no fluid resuscitation) and lactated Ringer`s (3 x shed blood volume). The left pulmonary hilum was cross clamped, and the animals were observed for 60 minutes. Systemic hemodynamics was evaluated using Swan-Ganz, arterial catheter, and ultrasonic flow probe. Systemic O(2)-derived variables were calculated. Ejection fraction was determined by two-dimensional echocardiography. Results: Fluid resuscitation improved the mean arterial pressure and systemic oxygen delivery. After pneumonectomy, no significant increase in right ventricular pressure was observed in the LR group. No signs of major ventricular dilation or changes in arterial oxygenation were observed. Conclusion: Our data suggest that pneumonectomy is not associated with early pulmonary hypertension; gentle fluid resuscitation improves cardiovascular performance and is not associated with an increase in right ventricular pressure.

Use of SVM Methods with Surface-Based Cortical and Volumetric Subcortical Measurements to Detect Alzheimer`s Disease

Here, we examine morphological changes in cortical thickness of patients with Alzheimer`s disease (AD) using image analysis algorithms for brain structure segmentation and study automatic classification of AD patients using cortical and volumetric data. Cortical thickness of AD patients (n = 14) was measured using MRI cortical surface-based analysis and compared with healthy subjects (n = 20). Data was analyzed using an automated algorithm for tissue segmentation and classification. A Support Vector Machine (SVM) was applied over the volumetric measurements of subcortical and cortical structures to separate AD patients from controls. The group analysis showed cortical thickness reduction in the superior temporal lobe, parahippocampal gyrus, and enthorhinal cortex in both hemispheres. We also found cortical thinning in the isthmus of cingulate gyrus and middle temporal gyrus at the right hemisphere, as well as a reduction of the cortical mantle in areas previously shown to be associated with AD. We also confirmed that automatic classification algorithms (SVM) could be helpful to distinguish AD patients from healthy controls. Moreover, the same areas implicated in the pathogenesis of AD were the main parameters driving the classification algorithm. While the patient sample used in this study was relatively small, we expect that using a database of regional volumes derived from MRI scans of a large number of subjects will increase the SVM power of AD patient identification.

Experimental models of sepsis and their clinical relevance

Sepsis remains a major cause of morbidity and mortality mainly because of sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have failed to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the potentials and limitations of various animal models of sepsis are discussed to clarify to which extent these findings are relevant to human sepsis. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models using different animal species including rats, mice, rabbits, dogs, pigs, sheep, and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be replaced by other methods. New therapeutic agents should be studied in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

Lymph Node Size in Rectal Cancer Following Neoadjuvant Chemoradiation-Can We Rely on Radiologic Nodal Staging After Chemoradiation?

OBJECTIVES: Local excision is currently being considered as an alternative strategy for ypT0-2 rectal cancer. However, patient selection is crucial to rule out nodal disease and is performed by radiologic studies that consider size as a surrogate marker for positive nodes. The purpose of this study was to determine the difference in size between metastatic and nonmetastatic nodes and the critical lymph node size after neoadjuvant chemoradiation therapy. METHODS: The 201 lymph nodes available from 31 patients with ypT0-2 rectal cancer were reviewed and measured. Lymph nodes were compared according to the presence of metastases and size. RESULTS: There was a mean of 6.5 lymph nodes per patient and 12 positive nodes of the 201 recovered (6%). Ninety-five percent of all lymph nodes were <5 mm, whereas 50% of positive lymph nodes were <3 mm. Metastatic lymph nodes were significantly greater in size (5.0 vs. 2.5mm; P = 0.02). Lymph nodes >4.5 mm had a greater risk of harboring metastases (P = 0.009). CONCLUSIONS: Patients with ypT0-2 rectal cancer following neoadjuvant chemoradiation have very small perirectal nodes. Individual metastatic lymph nodes are significantly larger. However, a significant number of lymph nodes after neoadjuvant chemoradiation (negative and positive) are <3 mm. Individual lymph node size is not a good predictor of nodal metastases and may lead to inaccurate radiologic staging.

Genitoperineal Injuries Associated With the Use of an Orthopedic Table With a Perineal Posttraction

Background: Surgical treatment of lower extremity fractures commonly involves the use of orthopedic table with perineal post for countertraction. However, prolonged application of the perineal post has been associated with significant complications. We describe our experience in the management of genitoperineal cutaneous injuries associated with the use of a traction table. Methods: Six patients with genitoperineal complications attributed to the use of a traction table were treated at our institution over a period of 2 years. The patient`s median age was 25 (range, 2028) years and all had fractures caused by motor vehicle collision. We evaluated the clinical presentation of these perineal injuries, operative time, therapeutic approach, clinical outcomes, and hospitalization time. Results. The mean operative time of the orthopedic surgery was 318 minutes 128 minutes (range, 185-540). All patients developed a partial-thickness necrotic area involving the perineum and scrotum in 2 days to 15 days (mean, 7 +/- 5.4) after the surgery. Three patients developed infection of the necrotic tissue. All patients underwent surgical debridement 16.5 days +/- 6.5 days (range, 13-29) after the orthopedic surgery and only one debridement procedure was nec-sure was possible in one case, and in the other cases the wound healed completely by second intention. The mean hospitalization time was 26.3 days +/- 9.7 days (range, 19-44). conclusion: Genitoperineal skin necrosis induced by perineal traction posttable is a morbid complication that demands surgical debridement and prolonged hospitalization for your treatment. There are many procedures available to reduce the risk of this complication that should be used more liberally by the orthopedic surgeons.

A randomized controlled trial comparing a computer-assisted insulin infusion protocol with a strict and a conventional protocol for glucose control in critically ill patients

Purpose: The objective of this study is to evaluate blood glucose (BG) control efficacy and safety of 3 insulin protocols in medical intensive care unit (MICU) patients. Methods: This was a multicenter randomized controlled trial involving 167 MICU patients with at least one BG measurement +/- 150 mg/dL and one or more of the following: mechanical ventilation, systemic inflammatory response syndrome, trauma, or burns. The interventions were computer-assisted insulin protocol (CAIP), with insulin infusion maintaining BG between 100 and 130 mg/dL; Leuven protocol, with insulin maintaining BG between 80 and 110 mg/dL; or conventional treatment-subcutaneous insulin if glucose > 150 mg/dL. The main efficacy outcome was the mean of patients` median BG, and the safety outcome was the incidence of hypoglycemia (<= 40 mg/dL). Results: The mean of patients` median BG was 125.0, 127.1, and 158.5 mg/dL for CAIP, Leuven, and conventional treatment, respectively (P = .34, CAIP vs Leuven; P < .001, CAIP vs conventional). In CAIP, 12 patients (21.4%) had at least one episode of hypoglycemia vs 24 (41.4%) in Leuven and 2 (3.8%) in conventional treatment (P = .02, CAIP vs Leuven; P = .006, CAIP vs conventional). Conclusions: The CAIP is safer than and as effective as the standard strict protocol for controlling glucose in MICU patients. Hypoglycemia was rare under conventional treatment. However, BG levels were higher than with IV insulin protocols. (C) 2009 Elsevier Inc. All rights reserved.

Primary immunodeficiencies unravel critical aspects of the pathophysiology of autoimmunity and of the genetics of autoimmune disease

Background Primary Immunodeficiencies (PIDs) represent unique opportunities to understand the operation of the human immune system. Accordingly, PIDs associated with autoimmune manifestations provide insights into the pathophysiology of autoimmunity as well as into the genetics of autoimmune diseases (AID). Epidemiological data show that there are PIDs systematically associated with AID, such as immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), Omenn syndrome, autoinunune polyendocrinopathy-candidiasis-ectodertnal dystrophy (APECED), autoinumine lymphoproliferative syndrome (ALPS), and C1q deficiency, while strong associations are seen with a handful of other deficits. Conclusion We interpret such stringent disease associations, together with a wealth of observations in experimental systems, as indicating first of all that natural tolerance to body components is an active, dominant process involving many of the components that ensure responsiveness, rather than, as previously believed, the result of the mere purge of autoreactivities. More precisely, it seems that deficits of Treg cell development, functions, numbers, and T cell receptor repertoire are among the main factors for autoimmunity pathogenesis in many (if not all) PIDs most frequently presenting with autoimmune features. Clearly, other pathophysiological mechanisms are also involved in autoimmunity, but these seem less critical in the process of self-tolerance. Comparing the clinical picture of IPEX cases with those, much less severe, of ALPS or APECED, provides some assessment of the relative importance of each set of mechanisms.

Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis

Introduction The protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi. Methods Seventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively). Results CLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours. Conclusions In an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.

Lung Pathology in Fatal Novel Human Influenza A (H1N1) Infection

Rationale: There are no reports of the systemic human pathology of the novel swine H1N1 influenza (S-OIV) infection. Objectives: The autopsy findings of 21 Brazilian patients with confirmed S-OIV infection are presented. These patients died in the winter of the southern hemisphere 2009 pandemic, with acute respiratory failure. Methods: Lung tissue was submitted to virologic and bacteriologic analysis with real-time reverse transcriptase polymerase chain reaction and electron microscopy. Expression of toll-like receptor (TLR)-3, IFN-gamma, tumor necrosis factor-alpha, CD8(+) T cells and granzyme B(+) cells in the lungs was investigated by immunohistochemistry. Measurements and Main Results: Patients were aged from 1 to 68 years (72% between 30 and 59 yr) and 12 were male. Sixteen patients had preexisting medical conditions. Diff use alveolar damage was present in 20 individuals. in six patients, diffuse alveolar damage was associated with necrotizing bronchiolitis and in five with extensive hemorrhage. There was also a cytopathic effect in the bronchial and alveolar epithelial cells, as well as necrosis, epithelial hyperplasia, and squamous metaplasia of the large airways. There was marked expression of TLR-3 and IFN-gamma and a large number of CD8(+) T cell sand granzyme B(+) cells within the lung tissue. Changes in other organs were mainly secondary to multiple organ failure. Conclusions: Autopsies have shown that the main pathological changes associated with S-OIV infection are localized to the lungs, where three distinct histological patterns can be identified. We also show evidence of ongoing pulmonary aberrant immune response. Our results reinforce the usefulness of autopsy in increasing the understanding of the novel human influenza A (H1N1) infection.

Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury

Introduction: Recruitment maneuvers (RMs) seem to be more effective in extrapulmonary acute lung injury (ALI), caused mainly by sepsis, than in pulmonary ALI. Nevertheless, the maintenance of adequate volemic status is particularly challenging in sepsis. Since the interaction between volemic status and RMs is not well established, we investigated the effects of RMs on lung and distal organs in the presence of hypovolemia, normovolemia, and hypervolemia in a model of extrapulmonary lung injury induced by sepsis. Methods: ALI was induced by cecal ligation and puncture surgery in 66 Wistar rats. After 48 h, animals were anesthetized, mechanically ventilated and randomly assigned to 3 volemic status (n = 22/group): 1) hypovolemia induced by blood drainage at mean arterial pressure (MAP)approximate to 70 mmHg; 2) normovolemia (MAP approximate to 100 mmHg), and 3) hypervolemia with colloid administration to achieve a MAP approximate to 130 mmHg. In each group, animals were further randomized to be recruited (CPAP = 40 cm H(2)O for 40 s) or not (NR) (n = 11/group), followed by 1 h of protective mechanical ventilation. Echocardiography, arterial blood gases, static lung elastance (Est, L), histology (light and electron microscopy), lung wet-to-dry (W/D) ratio, interleukin (IL)-6, IL-1 beta, caspase-3, type III procollagen (PCIII), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) mRNA expressions in lung tissue, as well as lung and distal organ epithelial cell apoptosis were analyzed. Results: We observed that: 1) hypervolemia increased lung W/D ratio with impairment of oxygenation and Est, L, and was associated with alveolar and endothelial cell damage and increased IL-6, VCAM-1, and ICAM-1 mRNA expressions; and 2) RM reduced alveolar collapse independent of volemic status. In hypervolemic animals, RM improved oxygenation above the levels observed with the use of positive-end expiratory pressure (PEEP), but increased lung injury and led to higher inflammatory and fibrogenetic responses. Conclusions: Volemic status should be taken into account during RMs, since in this sepsis-induced ALI model hypervolemia promoted and potentiated lung injury compared to hypo-and normovolemia.