The Regulation of Neutrophil Migration in Patients with Sepsis: The Complexity of the Molecular Mechanisms and Their Modulation in Sepsis and the Heterogeneity of Sepsis Patients.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Common causes include gram-negative and gram-positive bacteria as well as fungi. Neutrophils are among the first cells to arrive at an infection site where they function as important effector cells of the innate immune system and as regulators of the host immune response. The regulation of neutrophil migration is therefore important both for the infection-directed host response and for the development of organ dysfunctions in sepsis. Downregulation of CXCR4/CXCL12 stimulates neutrophil migration from the bone marrow. This is followed by transmigration/extravasation across the endothelial cell barrier at the infection site; this process is directed by adhesion molecules and various chemotactic gradients created by chemotactic cytokines, lipid mediators, bacterial peptides, and peptides from damaged cells. These mechanisms of neutrophil migration are modulated by sepsis, leading to reduced neutrophil migration and even reversed migration that contributes to distant organ failure. The sepsis-induced modulation seems to differ between neutrophil subsets. Furthermore, sepsis patients should be regarded as heterogeneous because neutrophil migration will possibly be further modulated by the infecting microorganisms, antimicrobial treatment, patient age/frailty/sex, other diseases (e.g., hematological malignancies and stem cell transplantation), and the metabolic status. The present review describes molecular mechanisms involved in the regulation of neutrophil migration; how these mechanisms are altered during sepsis; and how bacteria/fungi, antimicrobial treatment, and aging/frailty/comorbidity influence the regulation of neutrophil migration.

Systemic Metabolomic Profiles in Adult Patients with Bacterial Sepsis: Characterization of Patient Heterogeneity at the Time of Diagnosis.

Sepsis is a dysregulated host response to infection that causes potentially life-threatening organ dysfunction. We investigated the serum metabolomic profile at hospital admission for patients with bacterial sepsis. The study included 60 patients; 35 patients fulfilled the most recent 2016 Sepsis-3 criteria whereas the remaining 25 patients only fulfilled the previous Sepsis-2 criteria and could therefore be classified as having systemic inflammatory response syndrome (SIRS). A total of 1011 identified metabolites were detected in our serum samples. Ninety-seven metabolites differed significantly when comparing Sepsis-3 and Sepsis-2/SIRS patients; 40 of these metabolites constituted a heterogeneous group of amino acid metabolites/peptides. When comparing patients with and without bacteremia, we identified 51 metabolites that differed significantly, including 16 lipid metabolites and 11 amino acid metabolites. Furthermore, 42 metabolites showed a highly significant association with the maximal total Sequential Organ Failure Assessment (SOFA )score during the course of the disease (i.e., Pearson's correlation test, p-value < 0.005, and correlation factor > 0.6); these top-ranked metabolites included 23 amino acid metabolites and a subset of pregnenolone/progestin metabolites. Unsupervised hierarchical clustering analyses based on all 42 top-ranked SOFA correlated metabolites or the subset of 23 top-ranked amino acid metabolites showed that most Sepsis-3 patients differed from Sepsis-2/SIRS patients in their systemic metabolic profile at the time of hospital admission. However, a minority of Sepsis-3 patients showed similarities with the Sepsis-2/SIRS metabolic profile even though several of them showed a high total SOFA score. To conclude, Sepsis-3 patients are heterogeneous with regard to their metabolic profile at the time of hospitalization.

Weight gain during treatment course of allogenic hematopoietic stem cell transplantation in patients with hematological malignancies affects treatment outcome.

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for patients with hematological malignancies; however, allo-HSCT does not come without the cost of treatment-related morbidity and mortality. Early detection of risk factors could be helpful in identifying patients who could benefit from early interventions. Many patients gain weight during the allo-HSCT treatment, although little is known about the impact of weight gain. METHODS: Weight gain in 146 consecutively enrolled adult patients undergoing allo-HSCT was explored. RESULTS: In total, 141 patients (97%) gained weight along the course of allo-HSCT. Median weight increase was 4.8 kg (range 0.0-16.1 kg), with median increase in body weight 6.5% (range 0.0%-30.8%). Maximum weight increase was observed at day +7 (range day -8, +44). Weight gain was associated with increased incidence of acute graft-versus-host disease. Patients with weight gain >10% had a significantly greater 5-year mortality compared with those with lower weight gain (P = 0.031, rank sum test). CONCLUSIONS: Weight gain is a simple variable with the ability to provide prognostic information for patients undergoing allo-HSCT.

Endocan in Acute Leukemia: Current Knowledge and Future Perspectives.

Endocan is a soluble dermatan sulfate proteoglycan expressed by endothelial cells and detected in serum/plasma. Its expression is increased in tumors/tumor vessels in several human malignancies, and high expression (high serum/plasma levels or tumor levels) has an adverse prognostic impact in several malignancies. The p14 endocan degradation product can also be detected in serum/plasma, but previous clinical studies as well as previously unpublished results presented in this review suggest that endocan and p14 endocan fragment levels reflect different biological characteristics, and the endocan levels seem to reflect the disease heterogeneity in acute leukemia better than the p14 fragment levels. Furthermore, decreased systemic endocan levels in previously immunocompetent sepsis patients are associated with later severe respiratory complications, but it is not known whether this is true also for immunocompromised acute leukemia patients. Finally, endocan is associated with increased early nonrelapse mortality in (acute leukemia) patients receiving allogeneic stem cell transplantation, and this adverse prognostic impact seems to be independent of the adverse impact of excessive fluid overload. Systemic endocan levels may also become important to predict cytokine release syndrome after immunotherapy/haploidentical transplantation, and in the long-term follow-up of acute leukemia survivors with regard to cardiovascular risk. Therapeutic targeting of endocan is now possible, and the possible role of endocan in acute leukemia should be further investigated to clarify whether the therapeutic strategy should also be considered.

A woman in her sixties with epilepsy and syncope. / En kvinne i 60-årene med epilepsi og synkope.

BACKGROUND: A woman in her sixties had been diagnosed with generalised epilepsy twenty years earlier. The diagnosis was confirmed by EEG, and an MRI scan revealed hippocampal sclerosis, which is not uncommon in patients with epilepsy. Treatment with carbamazepine was initiated. CASE PRESENTATION: Due to a rise in the patient's cholesterol, carbamazepine was replaced with oxcarbazepine. At a follow-up, the patient reported a recent episode with loss of consciousness. Unstable epilepsy was suspected and the oxcarbazepine dose increased. The patient had had a minor stroke shortly before the check-up. As part of the diagnostic workup, a 24-hour ECG was performed. On removal of the apparatus, the patient described an episode with loss of consciousness that same morning. The ECG showed asystole at that point in time due to total AV block. A pacemaker was implanted, and the patient has had no episodes since. INTERPRETATION: The patient retrospectively reported recurrent episodes with loss of consciousness over many years. The diagnosis of epilepsy was convincing, but was the heart condition linked to her epilepsy, her medication or was it a separate entity? When seizures become more frequent or change character in a previously stabilised patient with epilepsy, it is important to look for non-epileptic causes, and cardiac arrhythmias should be high on the list.

Patients with Bacterial Sepsis Are Heterogeneous with Regard to Their Systemic Lipidomic Profiles.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In the present study, we investigated the systemic/serum lipidomic profile at the time of hospital admission for patients with bacterial sepsis. The study included 60 patients; 35 patients fulfilled the most recent 2016 Sepsis-3 criteria (referred to as Sepsis-3) whereas the remaining 25 patients had sepsis only according to the previous Sepsis-2 definition and could be classified as having Systemic Inflammatory Response Syndrome (SIRS). A total of 966 lipid metabolites were identified. Patients fulfilling the Sepsis-3 criteria differed from the Sepsis-2 patients with regard to only 15 lipid metabolites, and especially sphingolipids metabolism differed between these patient subsets. A total of only 43 metabolites differed between patients with and without bacteremia, including 12 lysophosphatidylcholines and 18 triacylglycerols (15 C18/C20 fatty acid metabolites decreased and three C14 myristate acid metabolites that were increased in bacteremia). Unsupervised hierarchical clustering analyses based on the identified sphingolipids, phosphatidylcholine and triacylglycerols showed that (i) the majority of Sepsis-3 patients differed from SIRS patients especially with regard to lysophosphatidylcholine levels; (ii) the minority of Sepsis-3 patients that clustered together with the majority of SIRS patients showed lower Sequential Organ Failure Assessment (SOFA) scores than the other Sepsis-3 patients; and (iii) the variation between the patients in the identified/altered sphingolipid and triacylglycerol metabolites further increased the heterogeneity of Sepsis-3 patients with regard to their systemic lipidomic profile at the time of diagnosis. To conclude, patients fulfilling the Sepsis-3 criteria differ with regard to their metabolic profile, and this variation depends on disease severity.

Carbapenem-Resistant Enterobacteriaceae-Implications for Treating Acute Leukemias, a Subgroup of Hematological Malignancies.

Acute leukemias (AL) are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. Patients with AL are highly susceptible to infectious diseases due to the disease itself, factors attributed to treatment, and specific individual risk factors. Enterobacteriaceae presence (e.g., Klebsiella pneumonia and Escherichia coli) is a frequent cause of bloodstream infections in AL patients. Carbapenem-resistant Enterobacteriaceae (CRE) is an emerging health problem worldwide; however, the incidence of CRE varies greatly between different regions. Carbapenem resistance in Enterobacteriaceae is caused by different mechanisms, and CRE may display various resistance profiles. Bacterial co-expression of genes conferring resistance to both broad-spectrum ß-lactam antibiotics (including carbapenems) and other classes of antibiotics may give rise to multidrug-resistant organisms (MDROs). The spread of CRE represents a major treatment challenge for clinicians due to lack of randomized clinical trials (RCTs), a limited number of antibiotics available, and the side-effects associated with them. Most research concerning CRE infections in AL patients are limited to case reports and retrospective reviews. Current research recommends treatment with older antibiotics, such as polymyxins, fosfomycin, older aminoglycosides, and in some cases carbapenems. To prevent the spread of resistant microbes, it is of pivotal interest to implement antibiotic stewardship to reduce broad-spectrum antibiotic treatment, but without giving too narrow a treatment to neutropenic infected patients.

Intermediate-High Risk Pulmonary Embolism: The Use of Riociguat and Inferior Vena Cava Filter in a Situation of Recurrent Embolism following Insufficient Anticoagulation and Fibrinolytic Therapy.

Pulmonary embolism (PE) is associated with serious morbidity and mortality. In this case report, we describe a hemodynamically stable patient with submassive PE and a large thrombus in the inferior vena cava (IVC) protruding into the right atrium (RA), complicated by severe respiratory failure, elevated troponin T (TnT), and right ventricular (RV) dysfunction. The patient was stratified as intermediate-high risk of early death. Important issues regarding the initial choice of anticoagulation, rescue thrombolytic therapy, and benefits of adding riociguat to stimulate the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway to improve the RV function are discussed. Finally, we address appropriate timing and the use of IVC filter in a situation of recurrent PE following anticoagulation and fibrinolytic therapy.

Epiglottitis. / Epiglottitt.

BACKGROUND: Acute epiglottitis in adults is a rare, potentially life-threatening condition caused by a bacterial infection in the epiglottis. Typical symptoms are fever, sore throat, and respiratory distress caused by upper airway obstruction. Proper treatment is needed for a good outcome. CASE PRESENTATION: We here present a 54-year-old female patient with acute epiglottitis. Her airway was secured by endotracheal intubation and she received antimicrobial therapy. She developed an abscess around the epiglottis that needed surgical drainage and tracheotomy. However, she fully recovered after nine days in hospital. INTERPRETATION: Acute epiglottitis in adults is a potentially life-threatening condition. The prognosis is good with proper treatment including selective airway intervention, antimicrobial therapy, and close monitoring.

Critical upper airway obstruction as the first symptom of acute myeloid leukemia - an anesthesiologic reminder.

Acute upper airway obstruction can be fatal. Early recognition of airway distress followed by diagnostic laryngoscopy and prompt intervention to secure airway control is crucial. We here present a 62-year old male patient who presented with cough and increasing respiratory distress for three weeks. Within the next 24 h, he developed symptoms of critical upper airway obstruction, endotracheal intubation was not possible, and an acute surgical tracheotomy was performed to retain patent airways. A computer tomography scan revealed severe laryngopharyngeal soft tissue thickening and upper airway obstruction caused by leukemic infiltration. He was diagnosed with acute leukemia and responded to induction chemotherapy. This case report points out the importance of establishing the diagnosis of critical upper airway obstruction in patients presenting with respiratory symptoms, and highlights the emergency management of airway obstruction due to malignant infiltration of leukemic blasts. laryngotracheal trauma, bleeding, tonsillar hypertrophy, paralysis of the vocal cords or folds, allergic reactions, and acute infections affecting the upper respiratory tract.1 We present a 62-year old male patient with cough and increasing respiratory distress for the last three weeks. Within 24 h in hospital, he developed symptoms of critical upper airway obstruction. Endotracheal intubation with the patient awakes and selfbreathing using a fiber optic scope was not possible, thus an acute surgical tracheotomy was performed to retain patent airways. Acute myeloid leukemia (AML) with leukemic infiltrations of the upper airways was found to be the underlying cause.

Febrile Neutropenia in Acute Leukemia. Epidemiology, Etiology, Pathophysiology and Treatment.

Acute leukemias are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. An important cause of both the latter is infectious complications. Patients with acute leukemia are highly susceptible to infectious diseases due to factors related to the disease itself, factors attributed to treatment, and specific individual risk factors in each patient. Patients with chemotherapy-induced neutropenia are at particularly high risk, and microbiological agents include viral, bacterial, and fungal agents. The etiology is often unknown in infectious complications, although adequate patient evaluation and sampling have diagnostic, prognostic and treatment-related consequences. Bacterial infections include a wide range of potential microbes, both Gram-negative and Gram-positive species, while fungal infections include both mold and yeast. A recurring problem is increasing resistance to antimicrobial agents, and in particular, this applies to extended-spectrum beta-lactamase resistance (ESBL), Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and even carbapenemase-producing Enterobacteriaceae (CPE). International guidelines for the treatment of sepsis in leukemia patients include the use of broad-spectrum Pseudomonas-acting antibiotics. However, one should implant the knowledge of local microbiological epidemiology and resistance conditions in treatment decisions. In this review, we discuss infectious diseases in acute leukemia with a major focus on febrile neutropenia and sepsis, and we problematize the diagnostic, prognostic, and therapeutic aspects of infectious complications in this patient group. Meticulously and thorough clinical and radiological examination combined with adequate microbiology samples are cornerstones of the examination. Diagnostic and prognostic evaluation includes patient review according to the multinational association for supportive care in cancer (MASCC) and sequential organ failure assessment (SOFA) scoring system. Antimicrobial treatments for important etiological agents are presented. The main challenge for reducing the spread of resistant microbes is to avoid unnecessary antibiotic treatment, but without giving to narrow treatment to the febrile neutropenic patient that reduce the prognosis.

A somnolent woman in her fifties with acute circulatory failure. / En somnolent kvinne i 50-årene med akutt sirkulasjonssvikt.

BACKGROUND: A woman in her fifties was admitted to hospital with decreased awareness and circulatory failure. She had been treated with left atrial cryoablation a few weeks before admission and had been cardioverted a few days after the procedure because of relapse of atrial fibrillation. CASE PRESENTATION: On admission, the patient had systolic blood pressure of 80 mm Hg and an ECG with broad QRS-complexes at 380 ms. We suspected intoxication and she was intubated to administer activated charcoal after gastric lavage. She was cardiovascularly unstable and in need of intravenous infusion of noradrenaline and adrenaline. Further investigations at her home suggested that she had poisoned herself with 4-5 g flecainide, 0.3 g oxazepam and 0.5 g meclizine. After administration of 500 mmol sodium bicarbonate and 5 mmol calcium chloride, the QRS complexes narrowed temporarily. On day 2, due to sustained bradycardia and hypotension despite receiving adrenergic medications, a temporary pacemaker was implanted, leading to improved heart rate and blood pressure. She experienced several complications including hypertensive pulmonary oedema, atrial fibrillation, extensively prolonged QT interval because of polypharmacy and Takotsubo cardiomyopathy. She was discharged from the hospital in good health on day 17. At a follow-up visit at the outpatient clinic 12 weeks later, cardiac function had normalised. The QT interval was now normal; however, there were persistent T-wave inversions in leads I, aVL and V4-6. INTERPRETATION: Flecainide blocks sodium channels in cardiomyocytes. Intoxication with flecainide is rare, with mortality rates of about 10 %. Sodium bicarbonate in larger doses has been reported to stabilise patients with flecainide intoxication due to modification of the binding of flecainide to sodium receptors in cardiomyocytes, and due to alkalisation which makes flecainide detach from sodium receptors. Our patient had a temporary effect with narrowing of QRS complexes after receiving sodium bicarbonate. She also showed a beneficial effect from implantation of a temporary pacemaker, although earlier case reports have described problems with high thresholds and capture failure.

Cytokine profiling and post-transfusion haemoglobin increment in patients with haematological diseases.

BACKGROUND AND OBJECTIVES: In a previous pilot study, we demonstrated significantly lower haemoglobin (Hb) increment after red-blood-cell (RBC) transfusions in febrile patients compared to patients without fever. The aim of this study was to examine associations between inflammatory mediators and post-transfusion haemoglobin increment in patients with haematological diseases. MATERIALS AND METHODS: Twenty-seven patients (eight women, 19 men), median age 56 years receiving RBC transfusion, were included in the study. Hb increment per unit transfused was corrected for estimated patient blood volume and the amount of Hb transfused. A wide spectrum of inflammatory mediators was determined by multiplex technology. Association between post-transfusion haemoglobin increment, plasma inflammatory mediators and patient characteristics was analysed using a mixed linear regression model. RESULTS: Febrile patients had significantly lower corrected Hb increment, significantly increased values of IL-6, IL-8, IL-10 and G-CSF, significantly reduced levels of CCL5 and CXCL10, and significantly higher pretransfusion levels of CRP. There was a significant association between pretransfusion CRP levels and corrected Hb increment for the whole patient cohort, but not within each of the two groups. Results demonstrated an association between haemoglobin increment, fever and inflammatory mediators. Febrile patients had a significantly lower corrected Hb increment compared to nonfebrile patients, when adjusting for mediators. When fever was kept constant, a significant negative association between haemoglobin increment and the proinflammatory mediators IL-6 and IL-8 was observed. CONCLUSION: Both fever and the inflammatory mediators IL-6 and IL-8 were negatively associated with post-transfusion haemoglobin increment.

Infective endocarditis in Western Norway: a 20-year retrospective survey.

BACKGROUND: To investigate epidemiological trends of infective endocarditis (IE) in western Norway a retrospective study was performed. METHODS: Characteristics of 706 IE admissions from 1996 to 2005 and 2006 to 2015 were analysed and compared using the Chi-square test for categorical variables and the t-test for age. Survival was analysed by multiple Cox regression and reported by the hazard ratio (HR). RESULTS: Mean annual incidence rates increased from 4.6 to 7.4 per 100,000 inhabitants (rate ratio: 1.97, 95% confidence interval: 1.52-2.56, p < .001). Non-viridans streptococci, enterococci and Staphylococcus aureus (S. aureus), were all independently associated with increased mortality. The frequency of IE caused by enterococci increased from 3.7 to 13.0% (p < .001). The proportion of intravenous drug users (IVDU) increased from 16.5 to 23.5% (p = .015) and had increasing aortic valve involvement (p = .023). Prosthetic valve endocarditis (PVE) constituted 30% of IE cases in both decades with biological PVE increasing from 9.4 to 22.1% (p < .001) and mechanical PVE decreasing from 18.7 to 8.9% (p < .001). In the last decade, valve replacement surgery was performed in 37.6% of the patients, of which 85.5% received a bioprosthesis. CONCLUSIONS: The incidence of IE increased significantly. Non-viridans streptococci, enterococci and S. aureus were all significantly associated with increased mortality. The increased number of enterococcal IE and the increased number of IVDUs with left-sided IE constituted new challenges. Biological implants were preferred in a majority of patients requiring surgery.

Cytokines, Adhesion Molecules, and Matrix Metalloproteases as Predisposing, Diagnostic, and Prognostic Factors in Venous Thrombosis.

The inflammatory response is a well-established part of, and a prerequisite for, venous thrombosis. To better understand the pathophysiology of venous thrombosis and to identify improved diagnostic biomarkers, further studies of the relationship between inflammation and coagulation are needed. We review previous studies concerning inflammatory biomarkers in venous thromboembolism, in particular cytokines, soluble adhesion molecules and matrix metalloproteases as predisposing, diagnostic and prognostic factors in venous thrombosis. Elevated cytokines and genetic alterations coding for cytokines are found in several patient cohorts which indicate that cytokines are involved as predisposing factors in venous thrombosis development. Increased levels of pro-inflammatory cytokines are detected both in animal models and in patients with acute venous thrombosis and clinical trials, although currently without evident diagnostic value. Adhesion molecules are crucial in the development of venous thrombosis, especially P-selectin seems important in initiating leukocyte accumulation and adhesion to endothelium for subsequent platelet accumulation. Several studies have demonstrated increased soluble P-selectin levels in patients with venous thrombosis, emphasizing its potential role as diagnostic marker and also as a therapeutic target. Matrix metalloproteases are essential effectors during venous thrombosis resolution and may impact vessel wall fibrosis, and together with their natural occurring inhibitors are crucial in acute and chronic thrombosis pathophysiology. Furthermore, studies in animal models of venous thrombosis have demonstrated anti-inflammatory treatment to be effective in terms of thrombus resolution and reduction of vessel wall damage, without increase in bleeding risk during the course of treatment. Thus, soluble mediators should be further investigated both as possible biomarkers and therapeutic targets in venous thromboembolic disease.

Microcirculation and red cell transfusion in patients with sepsis.

Early identification of sepsis followed by diagnostic blood cultures and prompt administration of appropriate intravenous antibiotics covering all likely pathogen remains the corner stone in the initial management of sepsis. Source control, obtained by harvesting microbiological cultures and removal or drainage of the infected foci, is mandatory. However, optimization of hemodynamically unstable patients including volume support supplemented with vasopressor, inotropic and transfusion of red blood cells (RBCs) in case of persistent hypoperfusion have the potential to reduce morbidity and mortality. Given the imbalance between the ability of the cardiovascular system to deliver enough oxygen to meet the oxygen demand, transfusion of RBCs should theoretically provide the ideal solution to the challenge. However, both changes in the septic patients' RBCs induced by endogenous factors as well as the storage lesion affecting transfused RBCs have negative effects on the microcirculation. RBC morphology, distribution of fatty acids on the membrane surface, RBC deformability needed for capillary circulation and the nitrogen oxide (NO) signaling systems are involved. Although these deteriorating effects develop during storage, transfusion of fresh RBCs has not proven to be beneficial, possibly due to limitations of the studies performed. Until better evidence exists, transfusion guidelines recommend a restrictive strategy of RBC transfusion i.e. transfuse when hemoglobin (Hb)<7g/dL in septic patients.

Non-curative surgery for aortoenteric fistula.

Graft infection with secondary aortic fistula is a rare complication following implantation of aortic prostheses, frequently occurring after emergency procedures and reoperations. The condition is associated with considerable morbidity and mortality. Curative treatment consists of explantation of the infected graft followed by fistula revision and implantation of a new graft in combination with antimicrobial therapy. Non-curative treatment with aortic stentgraft and long-term substitution treatment with antibiotics may be an option in cases where graft explantation is deemed too risky. We present an elderly patient with aortoenteric fistula following surgery for ruptured abdominal aortic aneurysm. Implantation of an aortic stentgraft and fistula revision was performed but the original aortic prosthesis was not explanted. The aortoenteric fistula recurred twice, but the patient has survived more than 12 years following non-curative surgery with good quality of life.

Arteriovenous fistula of the groin in a drug abuser with endocarditis.

Intravenous drug abusers commonly develop endocarditis due to injection of particulate matter that can cause endothelial damage to the valves. The frequent need to access the venous system can result in vascular traumas with potential complications including arteriovenous (AV) fistulas. Here, we present the case of an intravenous drug abuser with endocarditis and an unusually large AV fistula in the groin. The patient was successfully operated for endocarditis. However, the AV fistula was at the time not acknowledged. The combination of ileofemoral vein thrombosis and a large AV fistula led to pulmonary septic embolism and life-threating, right-sided heart failure. Computed tomography scan did not reveal the AV fistula, but suspicion was raised. Ultrasound diagnosed and revealed the magnitude of the AV fistula, and the patient was treated with a minimally invasive percutaneous technique.

Cardiac surgery for infective endocarditis in patients with intravenous drug use.

OBJECTIVES: Intravenous drug users have a high risk of infective endocarditis and reduced survival. Cardiac surgery may be recommended for these patients, but redo surgery is controversial. This study describes the characteristics and outcomes of intravenous drug users accepted for surgery during a 12-year period. METHODS: This retrospective study included 29 injecting drug users treated with valve surgery for endocarditis between January 2001 and December 2013 at a tertiary academic centre. Survival was assessed by Kaplan-Meier analysis. RESULTS: The median patient age was 36 (24-63) years and 27 patients (93%) were male. Staphylococcus aureus (52%) and Enterococcus faecalis (17%) were the most common microorganisms. Common illicit drugs were opioids (69%), amphetamines (52%) and benzodiazepines (24%). Mixed abuse was reported in 66% of patients. Seven patients (24%) had prior intracardial implants or native valve pathology. Twenty-five patients (86%) were positive for hepatitis C virus antibody, but none carried the human immunodeficiency virus. Twelve (41%) were homeless and 15 (52%) had poor dental hygiene. Three patients (10%) received medication-assisted rehabilitation before surgery. The main indications for surgery were regurgitation and secondary heart failure (86%), embolization (41%) and uncontrolled infection (24%). Aortic valve replacement was performed in 24 patients (83%), either as part of univalvular or multiple valve surgery. Seven patients (24%) had multivalvular endocarditis. All but 3 patients received biological valve prostheses. The 30-day mortality was 7% after first time surgery. During follow-up, 15 patients (52%) presented with reinfection: 10 (35%) were offered a second and 2 (7%) a third operation. Thirty-day mortality was 10% after redo surgery. Thirteen patients (45%) died within a median of 22 (0-84) months. Continued intravenous drug use was reported in 70 and 44% of patients after the first and second operation, respectively. CONCLUSIONS: Cardiac surgery for infective endocarditis has acceptable early postoperative results among intravenous drug users. The 2- and 5-year survival were 79 and 59%, respectively. The number of reinfections was high within 2 years, as continued drug use seems to be a major challenge for this group.