University Hospital Galway

PURPOSE: To update the World Society of the Abdominal Compartment Syndrome (WSACS) consensus definitions and management statements relating to intra-abdominal hypertension (IAH) and the abdominal compartment syndrome (ACS). METHODS: We conducted systematic or structured reviews to identify relevant studies relating to IAH or ACS. Updated consensus definitions and management statements were then derived using a modified Delphi method and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines, respectively. Quality of evidence was graded from high (A) to very low (D) and management statements from strong RECOMMENDATIONS (desirable effects clearly outweigh potential undesirable ones) to weaker SUGGESTIONS (potential risks and benefits of the intervention are less clear). RESULTS: In addition to reviewing the consensus definitions proposed in 2006, the WSACS defined the open abdomen, lateralization of the abdominal musculature, polycompartment syndrome, and abdominal compliance, and proposed an open abdomen classification system. RECOMMENDATIONS included intra-abdominal pressure (IAP) measurement, avoidance of sustained IAH, protocolized IAP monitoring and management, decompressive laparotomy for overt ACS, and negative pressure wound therapy and efforts to achieve same-hospital-stay fascial closure among patients with an open abdomen. SUGGESTIONS included use of medical therapies and percutaneous catheter drainage for treatment of IAH/ACS, considering the association between body position and IAP, attempts to avoid a positive fluid balance after initial patient resuscitation, use of enhanced ratios of plasma to red blood cells and prophylactic open abdominal strategies, and avoidance of routine early biologic mesh use among patients with open abdominal wounds. NO RECOMMENDATIONS were possible regarding monitoring of abdominal perfusion pressure or the use of diuretics, renal replacement therapies, albumin, or acute component-parts separation. CONCLUSION: Although IAH and ACS are common and frequently associated with poor outcomes, the overall quality of evidence available to guide development of RECOMMENDATIONS was generally low. Appropriately designed intervention trials are urgently needed for patients with IAH and ACS.

BACKGROUND: Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. METHODS: We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. RESULTS: The median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. CONCLUSIONS: Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.).

Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines.The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature.A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy.These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes.

We present a novel ultrasound-guided regional anaesthetic technique that may achieve complete paraesthesia of the hemithorax. This technique may be a viable alternative to current regional anaesthetic techniques such as thoracic paravertebral and central neuraxial blockade, which can be technically more challenging and have a higher potential side-effect profile. We performed the serratus block at two different levels in the midaxillary line on four female volunteers. We recorded the degree of paraesthesia obtained and performed fat-suppression magnetic resonance imaging and three-dimensional reconstructions of the spread of local anaesthetic in the serratus plane. All volunteers reported an effective block that provided long-lasting paraesthesia (750-840 min). There were no side-effects noted in this initial descriptive study. While these are preliminary findings, and must be confirmed in a clinical trial, they highlight the potential for the serratus plane block to provide analgesia following surgery on the thoracic wall. We suggest that this novel approach appears to be safe, effective, and easy to perform, and is associated with a low risk of side-effects.

Received from the Department of Anesthesia and Intensive Care, University College Hospital, Galway, Ireland; the Department of Anesthesia, Intensive Care and Pain Medicine, St. Vincent's University Hospital, Dublin, Ireland; and the Department of Anesthesia and Perioperative Medicine, University of Western Ontario, London, Ontario, Canada.THE purpose of this review is to evaluate recent developments in our understanding of the inflammatory response to cardiac surgery. Scientific knowledge in this field is continually expanding, potentially significant advances are regularly reported, and this area constitutes a major interface of clinical and basic scientific research. The review is divided into four major sections. The first section describes the pathophysiology of the inflammatory response to cardiac surgery. Factors that influence the extent of the inflammatory response, including the immunomodulatory effects of drugs commonly administered perioperatively, are discussed in the second section. The third section examines the evidence that the inflammatory response contributes to adverse perioperative events, in particular organ dysfunction, while the final section evaluates potential therapeutic strategies to control this response. The review concludes with a summary of potential future research directions and key deficiencies in our knowledge regarding the inflammatory response to cardiac surgery.Inflammation is the body's response to tissue injury and is a rapid, highly amplified, controlled humoral and cellular response. 1While the term “sepsis” has classically been utilized to imply a clinical response to infection, a similar response may arise in the absence of infection. 2In fact, patients who appear to have sepsis but have negative microbial cultures have similar morbidity and mortality rates to the respective culture-positive populations. 3This has led to the understanding that this process is a generalized, nonspecific inflammatory response to injury and prompted a diagnostic reclassification of these events into a pathophysiologic continuum by the American College of Chest Physicians–Society of Critical Care Medicine Consensus Conference Committee in 1991 (table 1). 2The term “systemic inflammatory response syndrome” (SIRS) has been proposed to describe the entry point to this continuum, an entity that overlaps with normal postoperative physiology. 2SIRS is a nonspecific, generalized inflammatory process, independent of the causative factors, and is of importance for several reasons. It is a sensitive if nonspecific indicator of injury. The classification of severity of SIRS into uncomplicated SIRS, sepsis, severe sepsis, and septic shock based on the existence of documented infection or hypotension has prognostic significance. 3A frequent complication of SIRS is the development of organ dysfunction, including acute lung injury, shock, renal failure, and multiple organ dysfunction syndrome (MODS). Finally, long-term survival in patients developing SIRS may also be adversely affected. This is well documented in the context of sepsis, with the risk of death increased for up to 5 yr after the septic episode. 4Cardiac surgery provokes a vigorous inflammatory response, which has important clinical implications. In the report from the Society of Thoracic Surgeons National Database, 20% (22,000 patients) of “low-risk” patients developed postoperative complications. 5The incidence of MODS following cardiopulmonary bypass (CPB) was 11%, with a mortality rate of 41% in these patients in another study. 6Acquired multiple organ dysfunction is the best predictor of mortality in cardiac surgical patients who require prolonged postoperative mechanical ventilation. 6Many aspects of a patient's risk of serious perioperative complications are perceived as being relatively fixed (genotype, preoperative health status, surgical difficulty, etc. ), but the degree to which these may be improved (e.g. , hemodynamic optimization using pharmacologic or mechanical support) is still under assessment. The contribution of the inflammatory response to patient outcome is potentially remediable and therefore deserves attention.Factors influencing incidence, severity, and clinical outcome of the inflammatory response, and in particular the reasons why certain patients develop life-threatening perioperative complications, are currently not well understood. Three separate perspectives contribute to our understanding of the link between the inflammatory response and adverse clinical sequelae. First, the complex interaction of humoral proinflammatory and antiinflammatory molecules may influence the clinical presentation and course of SIRS, with the balance of proinflammatory and antiinflammatory cytokines determining the clinical course following cardiac surgery. 7Alternatively, changes in the time course, magnitude, or patterns of cytokine release following CPB may contribute to abnormalities in the inflammatory response to cardiac surgery.Second, a “multiple-hit” scenario may be seen, whereby serious sequelae develop after cardiac surgery as a result of adverse events, such as infection or ongoing organ hypoperfusion. 1,8The combination results in the conversion of an inherently self-limiting, tightly controlled homeostatic response to an uncontrolled destructive process resulting in organ dysfunction. 1,8,9Potential mechanistic insights into the pathophysiologic basis for multiple hits include the ability of CPB to “prime” neutrophils, causing pulmonary leukosequestration, 10and enhanced cytotoxin release following a subsequent insult. 10Third, it has been suggested that there may be a fundamental misconception about the inflammatory response. The proinflammatory state, SIRS, may be only one aspect of a multifaceted response. The converse has been termed the compensatory antiinflammatory response syndrome. 11CPB-induced generalized immunosuppression may play an important role in the development of infectious complications. 12Cumulatively, these responses represent the body's attempt to reestablish homeostasis and may clinically manifest as predominantly proinflammatory (SIRS), antiinflammatory (compensatory antiinflammatory response syndrome), or an intermediate mixed response. 11As perioperative physicians, anesthesiologists contribute to the management of the patient when adverse sequelae of CPB may pose a significant threat. Anesthesiologists are well positioned to minimize the risk of adverse sequelae resulting from the inflammatory response to CPB by reducing perioperative risk factors. Many drugs administered during the perioperative period, particularly for the purposes of anesthesia and sedation, possess potentially important immunomodulatory effects. Anesthesiologists may be best placed to properly evaluate and eventually implement therapeutic strategies, particularly as many potentially useful therapies seem poised to enter the clinical arena. Finally, a thorough knowledge of all aspects of the inflammatory response to CPB is mandatory if the anesthesiologist is to realize the goal of minimizing perioperative risk.Nonspecific activators of the inflammatory response include surgical trauma, blood loss or transfusion, and hypothermia. In addition, CPB may specifically activate the inflammatory response via at least three distinct mechanisms (fig. 1). One mechanism involves direct “contact activation” of the immune system following exposure of blood to the foreign surfaces of the CPB circuit. A second mechanism involves ischemia–reperfusion injury to the brain, 13,14heart, 14,15lungs, 16kidney 17,18and liver 19as a result of aortic cross-clamping. Restoration of perfusion on release of the aortic cross-clamp is associated with activation of key indices of the inflammatory response. 20,21Endotoxemia may indirectly activate the inflammatory cascade. Splanchnic hypoperfusion, a common finding during and following CPB, 22may damage the mucosal barrier, allowing gut translocation of endotoxin. 23,24Systemic endotoxin concentrations correlate closely with the degree of cardiovascular dysfunction following CPB, 25,26while low preoperative serum immunoglobulin M antiendotoxin core antibody concentrations predict poor outcome. 27However, the importance of endotoxin in stimulating the inflammatory response to cardiac surgery remains in doubt, with conflicting evidence regarding the importance of gut translocation. 26,28In fact, endotoxin may be a contaminant of fluids, such as cardioplegia and circuit priming fluid, routinely used during CPB. 29The sole study to examine the incidence and time sequence of splanchnic hypoperfusion (as measured by intramucosal pH), gut permeability, and endotoxemia during CPB found no association between mucosal acidosis and either endotoxemia or intestinal permeability. 30Complement is activated during extracorporeal circulation, reperfusion of ischemic tissues, and heparin neutralization with protamine. 31Exposure of blood to the foreign surface of the extracorporeal circuit results in direct “contact” activation of the complement cascade, predominantly via the alternate pathway (fig. 2). 20,32,33The blood–gas interface of the CPB circuit may also play a role in complement activation. 34The formation of heparin–protamine complexes activates the complement cascade mainly via the classic (C4a) pathway. 32,35In the first 5 days following cardiac surgery, a second delayed increase in complement activation products is seen. 36This delayed activation of complement appears to be mediated by C reactive protein in response to heparin–protamine complexes. 36The central role of complement in the inflammatory response to cardiac surgery has been demonstrated by the effects of complement-specific inhibitors. Soluble human complement receptor type 1 attenuates lung and myocardial injury, 37while blockade of C3a formation prevents activation of neutrophils, monocytes and platelets in models of CPB. 38Anti-C5a monoclonal antibodies attenuate CPB-mediated pulmonary, 39myocardial, 40mesenteric, 41and microvascular 39,40dysfunction. Specific blockade of the alternative pathway of complement activation by monoclonal antibodies to properdin causes near complete inhibition of C3a and C5b-9 formation and dramatically reduces platelet and neutrophil activation. 42Recombinant soluble complement receptor 1, 43C3-binding cyclic synthetic peptide, 44and antihuman C5 monoclonal antibody 45all prevent up-regulation of adhesion molecules necessary for neutrophils to bind to the CPB circuit and vascular endothelium, a necessary step in the injury process. Finally, increased plasma concentrations of C5b-9, a terminal complex of complement proteins C5 to C9, are seen during CPB (fig. 2). Selective blockade of C5b-9 formation by antihuman C8 monoclonal antibody inhibits platelet but not leukocyte activation in a model of simulated extracorporeal circulation. 46The degree of complement activation in patients undergoing CPB has clinical significance. The degree of postoperative pulmonary shunt correlates with activation of the classic pathway by protamine–heparin complexes. 47Postoperative levels of C4d–C-reactive protein, a specific marker for C-reactive protein–mediated activation of complement, correlate with the incidence of postoperative arrhythmia following coronary artery bypass graft (CABG). 35,36Postoperative C3a concentrations may predict the probability of cardiac, pulmonary, renal, and hemostatic dysfunction 48and the likelihood of developing MODS in children. 33Strategies that improve CPB circuit biocompatibility reduce indices of complement activation and may decrease postoperative morbidity, particularly in high-risk patients. 49Anti-C5a antibody, which reduces sC5b-9 formation, significantly reduces myocardial injury, blood loss, and postoperative cognitive deficits in patients undergoing CPB. 50Cytokines are soluble proteins and polypeptides that act as paracrine messengers of the immune system and are produced by a large variety of cell types, including activated monocytes, tissue macrophages, lymphocytes, and endothelial cells (fig. 3). Individual cytokines may exert either proinflammatory or antiinflammatory effects. Cytokines are essential for immunologic and physiologic homeostasis, are normally subject to tight homeostatic control, and are produced in response to a variety of physiologic and pathologic stimuli.Proinflammatory cytokines play a pivotal role in stimulating the inflammatory process, with plasma concentrations of specific cytokines, such as interleukin-1β (IL-1β) and interleukin-6 (IL-6), predictive of outcome in certain critically ill patient subgroups (table 2). 51Tumor necrosis factor α (TNF-α) and IL-1β are elevated early following cardiac surgery, with IL-6 and IL-8 peaking later. 52,53While a direct cause-and-effect relation has not been demonstrated, elevations of proinflammatory cytokines have been strongly associated with adverse outcome following cardiac surgery. Patients who develop SIRS demonstrate significant elevations in cytokine concentrations compared to patients with an uncomplicated course following cardiac surgery. 54Within the subgroup of cardiac surgical patients who develop SIRS, nonsurvivors had dramatically higher IL-8 and IL-18 concentrations compared to survivors. 54In addition, serum concentrations of IL-6 correlate with mortality following pediatric cardiac surgery. 55The proinflammatory cytokine response to cardiac surgery is balanced by a phased antiinflammatory cytokine response, with soluble cytokine receptors, cytokine receptor antagonists, and antiinflammatory cytokines also produced in large quantities (table 3). 52Key antiinflammatory cytokines include interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1ra), TNF soluble receptors 1 and 2 (TNFsr 1 and 2), and transforming growth factor β. IL-10 is a potent inhibitor of the production of TNF-α, IL-1β, IL-6, and IL-8. 56While the specific role of other antiinflammatory mediators remains undefined, it has been suggested the clinical prognosis following CPB may depend on the balance between proinflammatory and antiinflammatory cytokines. 7Nitric oxide (NO) is a ubiquitous biologic mediator that acts as a physiologic regulator and can be responsible for tissue damage. Physiologic regulatory functions include endothelial-mediated vasodilation in both the systemic and pulmonary circulations, potentially significant immunomodulatory functions, as well as protean roles in nociception, memory, and erectile function. 57NO may have several protective roles in the inflammatory response. NO-induced vasodilation may prevent accumulation of injurious mediators at the endothelium (fig. 3). NO may scavenge free radicals and prevent up-regulation of neutrophil CD11/CD18 adhesion molecules. 58Supplementation of cardioplegia and perfusate with an NO precursor (arginine) or NO donor (SPM-5185) has beneficial effects on postreperfusion neutrophil accumulation, endothelial function, and myocardial performance following experimental myocardial ischemia, 59possibly by inhibiting neutrophil adherence and cytotoxicity. The release of NO during CPB appears to be dependent on the type of bypass flow, with attenuation of basal NO release during nonpulsatile flow leading to end-organ functional capillary closure as a result of diminished vessel wall shear stress. 60,61This release of NO is considered to be physiologic, produced by endothelial constitutive NO synthase (cNOS), 60,62and its release appears to be a function of both the frequency and amplitude of the pulsatile flow. 63The role of NO in the inflammatory response is complex, however, and NO has several potentially deleterious actions. Cytokine-induced decrements of myocardial function appear to be related to increases in myocardial inducible NO synthase (iNOS), 64which is up-regulated by CPB. 65Prevention of myocardial iNOS up-regulation may reduce hemodynamic instability post-CPB, 65while NOS inhibition can reverse refractory hypotension in established shock. NO is a highly reactive free radical and combines with a variety of molecules in vivo . While the free radical scavenging role of NO is generally protective, 66NO may combine with the free radical superoxide to form peroxynitrite, a more reactive and injurious free radical. 66,67Finally, NO appears to be a powerful direct cellular toxin, inactivating enzymes involved in glycolysis, the Krebs cycle, and the electron transport chain 67and reducing intracellular adenosine triphosphate and antioxidant concentrations, hence predisposing to cell death.The timing, source, and quantities of NO produced may be the key to dissecting these apparently paradoxical roles. NO is produced constitutively in small (picomolar) quantities by cNOS isoforms, such as the vascular endothelial isoform (ecNOS). ecNOS plays a pivotal role in the physiologic regulation of basal vascular tone, blood flow capillary integrity, and leukocyte and platelet adhesiveness to the endothelium. 57The activity of ecNOS appears to be inhibited in the earliest phases of the inflammatory response, allowing both unopposed vasoconstrictive influences and increased leukocyte and platelet adhesion to the endothelium. However, within 4–8 h, iNOS is produced in a wide variety of tissues, including vascular smooth muscle, hepatocytes, and Kupffer cells, 67,68and produces NO at much higher (nanomolar) quantities. Cytokines, particularly IL-1β, play a pivotal role in the process of NO-induced inflammatory dilatation. 69The proinflammatory response, once fully developed, represents a high-output NO state. 67In fact, exhaled NO following initiation of CPB may represent an index of severity of the inflammatory response, 70although this has been disputed. 71The coagulation–fibrinolytic cascades and the inflammatory response, while in many respects separate processes, are closely interconnected, with activation of coagulation a key component of the acute inflammatory response and vice versa . In this context, inflammation and coagulation should perhaps be considered different facets of the same host response to injury.The coagulation system has traditionally been divided (for conceptual and practical purposes) into the intrinsic and extrinsic pathways, both of which lead to a final common pathway, and result, via thrombin generation, in the formation of an insoluble fibrin clot. Activation of coagulation after CPB had been thought to be predominantly due to activation of the intrinsic pathway via the contact system. In this paradigm, plasma factor XII was pivotal to this process, becoming adsorbed and activated on contact with the CPB circuit. However, patients with congenital deficiency of factor XII still generate thrombin following CPB. 72This suggests that the extrinsic pathway, which requires expression and activation of tissue factor, perhaps in response to inflammatory stimuli and oxidative or shear stress, may also be involved. 73Hemostasis is mediated by a balance of procoagulant and anticoagulant forces, which normally coexist in a delicate balance. The coagulation cascade consists of inactive circulating precursors, which are sequentially activated via enzymatic cleavage, yielding an active serine protease that hydrolyses the next factor in the cascade. Thrombin, the end product, catalyzes the formation of insoluble fibrin from fibrinogen, which form the strands that bind the platelet plug. This process is normally controlled and limited to discrete sites of injury by modulators, including plasminogen activators, thrombomodulin, proteins C and S, and serine protease inhibitors such as antithrombin III. 74The fibrinolytic cascade, activated during coagulation, results in the formation of plasmin, which splits fibrinogen and fibrin, remodelling the formed clot and later removing the thrombus when the endothelium heals.Several specific points regarding the complex interrelation between coagulation and inflammation, in the context of CPB, deserve attention. The endothelium is intricately involved in both processes (see Endothelium). Proinflammatory cytokines play a key role in initiating the coagulation process locally at sites of inflammation, by activation of the endothelium, induction of the expression of tissue factor, the expression of leukocyte adhesion molecules on the cell and stimulating production of factors. with of expression and of the fibrinolytic and protein C anticoagulant pathways, the balance between procoagulant and anticoagulant resulting in a procoagulant state. coagulation system in on the inflammatory response. activation at sites of tissue injury results in the release of multiple mediators that tissue key coagulation such as thrombin and factor have proinflammatory Thrombin, formed following activation of the coagulation cascade, several cell and which are responsible for the of the and the tissue process. and which are used to coagulation in all patients undergoing cardiac surgery, may have important immunomodulatory effects. appears to possess important antiinflammatory effects. neutralization of heparin may result in multiple cardiovascular including increased pulmonary artery and and blood myocardial cardiac and systemic vascular by has adverse the heparin–protamine complex is particularly The heparin–protamine interaction activates the inflammatory response by several including complement and oxide and antibody release of may result in severe pulmonary a of severe may result from the balance of and is in CPB patients. Activation of such as thrombin of anticoagulant drugs to CPB to prevent blood from on contact with the extracorporeal circuit. In addition, the of during CPB appears to contribute to the postoperative commonly seen in these patients. vascular injury following CPB may result in uncontrolled platelet thrombin generation, and resulting fibrin in the may flow and end-organ which may to MODS and vascular endothelium is a in cellular and organ function a barrier, as was once It is involved in a variety of physiologic and pathologic processes and has as the central of many of the biologic events that the perioperative course of the cardiac surgical The endothelium vascular and permeability, coagulation and and the of into of inflammation, the expression of surface proteins and of soluble inflammatory response to CPB is by a of endothelial activation and endothelial dysfunction. including and IL-1β, bind to specific receptors on the endothelium, initiating pathways, which in activate a specific of within the of the endothelial termed activation The factor plays a pivotal role in the process. it from the protein to the endothelial cell with specific and the of the basal resulting in the of the activation process results in the of including adhesion molecules (e.g. , adhesion and cytokines (e.g. , for endothelial cell a process that and at on the activated endothelial cell plays a pivotal role in the inflammatory and coagulation by proteins central to the activation of coagulation and cell adhesion expression the interaction between the neutrophil and the endothelial cell (see The resulting in neutrophil and This the endothelium, causing capillary and injury results in the expression of tissue factor, by IL-1β and TNF-α, which activates the extrinsic pathway of coagulation may result in addition, protein a key regulator of is in inflammatory by TNF-α, the balance a procoagulant state. endothelium plays a central role in the of following CPB. regulation of vascular (fig. is mediated via a variety of and such as factor, and increase in pulmonary vascular following CPB is to NO release from pulmonary endothelium is by NO complex between endothelial function, inflammation, and in the of adverse cardiovascular in NO appear to these particular the inflammatory response to cardiac surgery may increase the risk of a postoperative cardiac Proinflammatory cytokines and endotoxin can and the endothelium may its ability to to circulating or of demonstrate that IL-1β, TNF-α, and endotoxin prolonged but of endothelial termed cytokines production of NO and a of the and effects of NO may myocardial perfusion to unopposed and may the association between an acute inflammatory and a increase in the risk of a cardiovascular addition, endothelial dysfunction may the long-term of cardiac surgery, particularly by to the development of at graft sites as a result of by the of of including paradoxical responses , are in the earliest of coronary artery clinical demonstrate that this is associated with an increased rate of cardiovascular dysfunction activates the inflammatory response, and platelets to the which may the formation of process is particularly at sites of blood flow such as at graft is by the of dysfunction in patients is in large due to a of this which have been demonstrated to endothelial function, in by of endothelial function results in improved myocardial myocardial ischemia, and of process of adhesion is an essential component of the inflammatory response leading to endothelial damage and is well distinct phases of and adhesion (fig. the the leukocyte at with the in the of the In the first the neutrophil is to the state, in which it the endothelium. is mediated by the expression of a of adhesion molecules as and are on the endothelium, and is on the are involved in the formation of between the endothelium and the which the of the leukocyte the blood vessel on activation of the complement cascade following contact with the extracorporeal circulation, is a potent of is in and the plasma by after endothelial cell activation. may the in the pulmonary circulation, which following initiation of CPB. process of

BACKGROUND: The transversus abdominis plane (TAP) block is a novel approach for blocking the abdominal wall neural afferents via the bilateral lumbar triangles of Petit. We evaluated its analgesic efficacy in patients during the first 24 postoperative hours after abdominal surgery, in a randomized, controlled, double-blind clinical trial. METHODS: Thirty-two adults undergoing large bowel resection via a midline abdominal incision were randomized to receive standard care, including patient-controlled morphine analgesia and regular nonsteroidal antiinflammatory drugs and acetaminophen (n = 16), or to undergo TAP block (n = 16) in addition to standard care (n = 16). After induction of anesthesia, 20 mL of 0.375% levobupivacaine was deposited into the transversus abdominis neuro-fascial plane via the bilateral lumbar triangles of Petit. Each patient was assessed by a blinded investigator in the postanesthesia care unit and at 2, 4, 6, and 24 h postoperatively. RESULTS: The TAP block reduced visual analog scale pain scores (TAP versus control, mean +/- sd) on emergence (1 +/- 1.4 vs 6.6 +/- 2.8, P < 0.05), and at all postoperative time points, including at 24 h (1.7 +/- 1.7 vs 3.1 +/- 1.5, P < 0.05). Morphine requirements in the first 24 postoperative hours were also reduced (21.9 +/- 8.9 mg vs 80.4 +/- 19.2 mg, P < 0.05). There were no complications attributable to the TAP block. All TAP patients reported high levels of satisfaction with their postoperative analgesic regimen. CONCLUSIONS: The TAP block provided highly effective postoperative analgesia in the first 24 postoperative hours after major abdominal surgery.

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.

Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.

Abstract Background Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ≥30 L/min; 2) use PaO2:Fi O2 ≤ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:Fi O2 ≤ 315 (if oxygen saturation as measured by pulse oximetry is ≤97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

In Brief Objective: The development of clinically validated biomarkers for cancer has remained an insurmountable task despite other advances in the field of cancer molecular biology. Mi(cro)RNAs have many characteristics of an ideal biomarker most notably their inherent stability and resilience. Recent blood-based miRNA profiling studies, reporting their presence in serum and plasma, have generated the concept that circulating miRNAs hold much potential as novel noninvasive biomarkers for cancer and other disease processes. The objective of this study was to investigate the potential of circulating microRNAs as novel breast cancer biomarkers. Methods: Using a novel approach to extract miRNAs from the circulation followed by real-time quantitative polymerase chain reaction analysis, levels of a panel of 7 candidate miRNAs were quantified in tissue and blood specimens of 148 patients with breast cancer and 44 age-matched and disease free control individuals. Results: We report that cancer-specific miRNAs were detected and significantly altered in the circulation of breast cancer patients, and that increased systemic miR-195 levels in breast cancer patients were reflected in breast tumors. Furthermore, we identified that circulating levels of miR-195 and let-7a decreased in cancer patients postoperatively, to levels comparable with control subjects, following curative tumor resection. Finally, we found that specific circulating miRNAs correlated with certain clinicopathological variables, namely nodal status and estrogen receptor status. Conclusion: These findings suggest that systemic miRNAs have potential use as novel breast cancer biomarkers and may prove useful in clinical management during the perioperative period. The development of clinically validated biomarkers for cancer has remained an insurmountable task despite other advances in the field of cancer molecular biology. We report that cancer-specific miRNAs are detectable and altered in the circulation of breast cancer patients; in particular, systemic miR-195 levels in breast cancer patients reflect many properties of an ideal biomarker.

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure <65 mm Hg at least once, <90 mm Hg for >30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation <80%) or cardiac arrest. The secondary outcomes included intensive care unit mortality. Results: Of 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%. Conclusions and Relevance: In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events-in particular cardiovascular instability-were observed frequently.

BACKGROUND: The transversus abdominis plane (TAP) block is an effective method of providing postoperative analgesia in patients undergoing midline abdominal wall incisions. We evaluated its analgesic efficacy over the first 48 postoperative hours after cesarean delivery performed through a Pfannensteil incision, in a randomized controlled, double-blind, clinical trial. METHODS: Fifty women undergoing elective cesarean delivery were randomized to undergo TAP block with ropivacaine (n = 25) versus placebo (n = 25), in addition to standard postoperative analgesia comprising patient-controlled IV morphine analgesia and regular diclofenac and acetaminophen. All patients received a standard spinal anesthetic, and at the end of surgery, a bilateral TAP block was performed using 1.5 mg/kg ropivacaine (to a maximal dose of 150 mg) or saline on each side. Each patient was assessed postoperatively by a blinded investigator: in the postanesthesia care unit and at 2, 4, 6, 12, 24, 36, and 48 h postoperatively. RESULTS: The TAP block with ropivacaine compared with placebo reduced postoperative visual analog scale pain scores. Mean (+/- sd) total morphine requirements in the first 48 postoperative hours were also reduced (66 +/- 26 vs 18 +/- 14 mg, P < 0.001), as was the 12-h interval morphine consumption up to 36 h postoperatively. The incidence of sedation was reduced in patients undergoing TAP blockade. There were no complications attributable to the TAP block. CONCLUSIONS: The TAP block, as a component of a multimodal analgesic regimen, provided superior analgesia when compared with placebo block up to 48 postoperative hours after elective cesarean delivery.

Coronavirus disease 2019 (COVID-19) is a declared global pandemic. There are multiple parameters of the clinical course and management of the COVID-19 that need optimization. A hindrance to this development is the vast amount of misinformation present due to scarcely sourced manuscript preprints and social media. This literature review aims to presents accredited and the most current studies pertaining to the basic sciences of SARS-CoV-2, clinical presentation and disease course of COVID-19, public health interventions, and current epidemiological developments. The review on basic sciences aims to clarify the jargon in virology, describe the virion structure of SARS-CoV-2 and present pertinent details relevant to clinical practice. Another component discussed is the brief history on the series of experiments used to explore the origins and evolution of the phylogeny of the viral genome of SARS-CoV-2. Additionally, the clinical and epidemiological differences between COVID-19 and other infections causing outbreaks (SARS, MERS, H1N1) are elucidated. Emphasis is placed on evidence-based medicine to evaluate the frequency of presentation of various symptoms to create a stratification system of the most important epidemiological risk factors for COVID-19. These can be used to triage and expedite risk assessment. Furthermore, the limitations and statistical strength of the diagnostic tools currently in clinical practice are evaluated. Criteria on rapid screening, discharge from hospital and discontinuation of self-quarantine are clarified. Epidemiological factors influencing the rapid rate of spread of the SARS-CoV-2 virus are described. Accurate information pertinent to improving prevention strategies is also discussed. The penultimate portion of the review aims to explain the involvement of micronutrients such as vitamin C and vitamin D in COVID19 treatment and prophylaxis. Furthermore, the biochemistry of the major candidates for novel therapies is briefly reviewed and a summary of their current status in the clinical trials is presented. Lastly, the current scientific data and status of governing bodies such as the Center of Disease Control (CDC) and the WHO on the usage of controversial therapies such as angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) (Ibuprofen), and corticosteroids usage in COVID-19 are discussed. The composite collection of accredited studies on each of these subtopics of COVID-19 within this review will enable clarification and focus on the current status and direction in the planning of the management of this global pandemic.

Aims: To determine the ranges of pre-test probability (PTP) of coronary artery disease (CAD) in which stress electrocardiogram (ECG), stress echocardiography, coronary computed tomography angiography (CCTA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance (CMR) can reclassify patients into a post-test probability that defines (>85%) or excludes (<15%) anatomically (defined by visual evaluation of invasive coronary angiography [ICA]) and functionally (defined by a fractional flow reserve [FFR] ≤0.8) significant CAD. Methods and results: A broad search in electronic databases until August 2017 was performed. Studies on the aforementioned techniques in >100 patients with stable CAD that utilized either ICA or ICA with FFR measurement as reference, were included. Study-level data was pooled using a hierarchical bivariate random-effects model and likelihood ratios were obtained for each technique. The PTP ranges for each technique to rule-in or rule-out significant CAD were defined. A total of 28 664 patients from 132 studies that used ICA as reference and 4131 from 23 studies using FFR, were analysed. Stress ECG can rule-in and rule-out anatomically significant CAD only when PTP is ≥80% (76-83) and ≤19% (15-25), respectively. Coronary computed tomography angiography is able to rule-in anatomic CAD at a PTP ≥58% (45-70) and rule-out at a PTP ≤80% (65-94). The corresponding PTP values for functionally significant CAD were ≥75% (67-83) and ≤57% (40-72) for CCTA, and ≥71% (59-81) and ≤27 (24-31) for ICA, demonstrating poorer performance of anatomic imaging against FFR. In contrast, functional imaging techniques (PET, stress CMR, and SPECT) are able to rule-in functionally significant CAD when PTP is ≥46-59% and rule-out when PTP is ≤34-57%. Conclusion: The various diagnostic modalities have different optimal performance ranges for the detection of anatomically and functionally significant CAD. Stress ECG appears to have very limited diagnostic power. The selection of a diagnostic technique for any given patient to rule-in or rule-out CAD should be based on the optimal PTP range for each test and on the assumed reference standard.

Introduction: Intravenous(IV) immunoglobulin(Ig) treatment is known to alleviate behavioral deficits in the experimentally induced model of sepsis. To delineate the mechanisms by which IVIg treatment prevents neuronal dysfunction, an array of immunological and apoptosis markers was investigated. Methods: Sepsis was induced by cecal ligation perforation(CLP) in rats. The animals were divided into five groups; sham, control, CLP + saline, CLP + immunoglobulin G IgG(250 mg/kg,iv), and CLP + immunoglobulins enriched with immunoglobulin M-IgGAM(250 mg/kg,iv). Blood and brain samples were taken in two sets of experiments after CLP to see the early(24 hrs) and late(10 days) effects of treatment. Total complement activity, complement 3(C3) and soluble complement C5b-9 levels were measured in sera of rats using ELISA-based methods. Cerebral complement content was analyzed by Western Blot. Immune cell infiltration and gliosis were examined by immunohistochemistry using cluster of differentiation 3, CD4, CD8, CD11b, CD19 and glial fibrillary acidic protein antibodies. Apoptotic neuronal death was investigated by TUNEL staining and Western Blot-based semi-quantitative evaluation of brain homogenates by bax and bcl-2 antibodies. Results: IV IgG and IgGAM administration significantly reduced systemic complement activity but increased serum C3 and soluble C5b-9 levels. Likewise, Western Blot data showed slightly increased C5b-9 expression and significantly reduced C1q expression in brain samples of IgGAM-treated but not IgG-treated septic rats especially in the first day of administration. No cerebral cellular infiltrates were observed in treated and non-treated septic rats. By contrast, IV IgG and IgGAM treatment induced considerable amelioration in glial cell proliferation which was increased in non-treated rats. IgG and IgGAM treated rats exhibited significantly reduced numbers of apoptotic neurons and cerebral expression levels of bax and bcl-2 as compared to nontreated rats. Conclusions: We suggest that IV IgG and IgGAM administration ameliorates neuronal dysfunction and behavioral deficits by reducing apoptotic cell death and glial cell proliferation. IgGAM treatment might be suppressing classical complement pathway by reducing C1q expression.

Coronavirus (COVID-19) is highly infectious agent that causes fatal respiratory illnesses, which is of great global public health concern. Currently, there is no effective vaccine for tackling this COVID19 pandemic where disease countermeasures rely upon preventing or slowing person-to-person transmission. Specifically, there is increasing efforts to prevent or reduce transmission to front-line healthcare workers (HCW). However, there is growing international concern regarding the shortage in supply chain of critical one-time-use personal and protective equipment (PPE). PPE are heat sensitive and are not, by their manufacturer's design, intended for reprocessing. Most conventional sterilization technologies used in hospitals, or in terminal medical device sterilization providers, cannot effectively reprocess PPE due to the nature and severity of sterilization modalities. Contingency planning for PPE stock shortage is important. Solutions in the Republic of Ireland include use of smart communication channels to improve supply chain, bespoke production of PPE to meets gaps, along with least preferred option, use of sterilization or high-level disinfection for PPE reprocessing. Reprocessing PPE must consider material composition, functionality post treatment, along with appropriate disinfection. Following original manufacturer of PPE and regulatory guidance is important. Technologies deployed in the US, and for deployment in the Republic of Ireland, are eco-friendly, namely vaporised hydrogen peroxide (VH2O2), such as for filtering facepiece respirators and UV irradiation and High-level liquid disinfection (Actichlor+) is also been pursed in Ireland. Safeguarding supply chain of PPE will sustain vital healthcare provision and will help reduce mortality.

INTRODUCTION: Breast cancer is a heterogeneous disease encompassing a number of phenotypically diverse tumours. Expression levels of the oestrogen, progesterone and HER2/neu receptors which characterize clinically distinct breast tumours have been shown to change during disease progression and in response to systemic therapies. Mi(cro)RNAs play critical roles in diverse biological processes and are aberrantly expressed in several human neoplasms including breast cancer, where they function as regulators of tumour behaviour and progression. The aims of this study were to identify miRNA signatures that accurately predict the oestrogen receptor (ER), progesterone receptor (PR) and HER2/neu receptor status of breast cancer patients to provide insight into the regulation of breast cancer phenotypes and progression. METHODS: Expression profiling of 453 miRNAs was performed in 29 early-stage breast cancer specimens. miRNA signatures associated with ER, PR and HER2/neu status were generated using artificial neural networks (ANN), and expression of specific miRNAs was validated using RQ-PCR. RESULTS: Stepwise ANN analysis identified predictive miRNA signatures corresponding with oestrogen (miR-342, miR-299, miR-217, miR-190, miR-135b, miR-218), progesterone (miR-520g, miR-377, miR-527-518a, miR-520f-520c) and HER2/neu (miR-520d, miR-181c, miR-302c, miR-376b, miR-30e) receptor status. MiR-342 and miR-520g expression was further analysed in 95 breast tumours. MiR-342 expression was highest in ER and HER2/neu-positive luminal B tumours and lowest in triple-negative tumours. MiR-520g expression was elevated in ER and PR-negative tumours. CONCLUSIONS: This study demonstrates that ANN analysis reliably identifies biologically relevant miRNAs associated with specific breast cancer phenotypes. The association of specific miRNAs with ER, PR and HER2/neu status indicates a role for these miRNAs in disease classification of breast cancer. Decreased expression of miR-342 in the therapeutically challenging triple-negative breast tumours, increased miR-342 expression in the luminal B tumours, and downregulated miR-520g in ER and PR-positive tumours indicates that not only is dysregulated miRNA expression a marker for poorer prognosis breast cancer, but that it could also present an attractive target for therapeutic intervention.

INTRODUCTION: Laparoscopic cholecystectomy (LC) has become a popular alternative to open cholecystectomy (OC) in the treatment of acute cholecystitis (AC). Laparoscopic cholecystectomy (LC) is now considered the gold standard of therapy for symptomatic cholelithiasis and chronic cholecystitis. However no definitive data on its use in AC has been published. CIAO and CIAOW studies demonstrated 48.7% of AC were still operated with the open technique. The aim of the present meta-analysis is to compare OC and LC in AC. MATERIAL AND METHODS: A systematic-review with meta-analysis and meta-regression of trials comparing open vs. laparoscopic cholecystectomy in patients with AC was performed. Electronic searches were performed using Medline, Embase, PubMed, Cochrane Central Register of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR) and CINAHL. RESULTS: Ten trials have been included with a total of 1248 patients: 677 in the LC and 697 into the OC groups. The post-operative morbidity rate was half with LC (OR = 0.46). The post-operative wound infection and pneumonia rates were reduced by LC (OR 0.54 and 0.51 respectively). The post-operative mortality rate was reduced by LC (OR = 0.2). The mean postoperative hospital stay was significantly shortened in the LC group (MD = -4.74 days). There were no significant differences in the bile leakage rate, intraoperative blood loss and operative times. CONCLUSIONS: In acute cholecystitis, post-operative morbidity, mortality and hospital stay were reduced by laparoscopic cholecystectomy. Moreover pneumonia and wound infection rate were reduced by LC. Severe hemorrhage and bile leakage rates were not influenced by the technique. Cholecystectomy in acute cholecystitis should be attempted laparoscopically first.

OBJECTIVE: To investigate serum cardiac troponin I, a sensitive marker of cardiac myocyte damage, in normal pregnancy and pregnancies complicated by hypertension with and without significant proteinuria. DESIGN: Prospective cross sectional study. SETTING: University hospital delivery suite. SAMPLE: Serum samples obtained from women in normal pregnancy and in pregnancies complicated by hypertension with and without significant proteinuria. METHOD: Women with hypertension in pregnancy (at least two readings of systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg) (n = 26) and normotensive women (n = 43) were included in the study. Serum cardiac troponin I was measured using Beckman Access immunoassay. MAIN OUTCOME MEASURE: Serum cardiac troponin I level in the pregnancies complicated by hypertension (with and without significant proteinuria) compared with the levels measured in normotensive women. RESULTS: The median serum cardiac troponin I level in pregnancies complicated by hypertension was 0.118 ng/mL (n = 26) which was significantly greater than that measured in samples obtained from normotensive women in pregnancy (0.03 ng/mL; n = 43) (P < 0.0001). There were higher median serum cardiac troponin I levels in hypertensive women with significant proteinuria (0.155 ng/mL; n = 6), compared with those without proteinuria (0.089 ng/mL; n = 20; P = 0.03). CONCLUSION: Serum cardiac troponin I is elevated in women with hypertensive disorders of pregnancy indicating some degree of cardiac myofibrillary damage in these disorders.