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Patients with chronic kidney disease (CKD) are at an increased risk of thromboembolic complications, including myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism. These complications lead to increased mortality. Evidence points to the key role of CKD-associated dysbiosis and its effect via the generation of gut microbial metabolites in inducing the prothrombotic phenotype. This phenomenon is known as thrombolome, a panel of intestinal bacteria-derived uremic toxins that enhance thrombosis via increased tissue factor expression, platelet hyperactivity, microparticles release, and endothelial dysfunction. This review discusses the role of uremic toxins derived from gut-microbiota metabolism of dietary tryptophan (indoxyl sulfate (IS), indole-3-acetic acid (IAA), kynurenine (KYN)), phenylalanine/tyrosine (p-cresol sulfate (PCS), p-cresol glucuronide (PCG), phenylacetylglutamine (PAGln)) and choline/phosphatidylcholine (trimethylamine N-oxide (TMAO)) in spontaneously induced thrombosis. The increase in the generation of gut microbial uremic toxins, the activation of aryl hydrocarbon (AhRs) and platelet adrenergic (ARs) receptors, and the nuclear factor kappa B (NF-κB) signaling pathway can serve as potential targets during the prevention of thromboembolic events. They can also help create a new therapeutic approach in the CKD population.

Numerous algorithms based on patient genetic variants have been established with the aim of reducing the risk of GI bleeding and thromboembolism during warfarin administration. However, approximately 35 % of individual warfarin sensitivity still remains unexplained. Few of warfarin algorithms take into account gut microbiota profiles. The identification of certain microbiome will provide new targets and new strategies for reducing the risk of bleeding and thromboembolism during warfarin administration. In this study, we collected plasma and stool samples from 200 inpatients undergoing heart valve replacement (HVR), which were classified as low responder (LR), high responder (HR) and normal responder (NR). Significant differences were observed in the diversity and relative abundance of the gut microbiota among the three groups. The genus Escherichia-Shigella was enriched significantly in the LRs (P = 3.189e -11 ), while the genus Enterococcus was enriched significantly in the HRs (P = 1.249e -11 ). The amount of VK2 synthesized by gut microbiota in LR group was much higher than that in HR group (P = 0.005). Whole genome shotgun sequencing indicated that the relative abundance of enzymes and modules associated with VK biosynthesis was significantly higher in LRs than in HRs or NRs. The 12 microbial markers were identified through tenfold cross-validation with a random forest model. The results provided a new microbial diagnostic model that can be used to inform modulation of warfarin dosage on the basis of patient intestinal flora composition., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Embolic events from vegetations are commonly accepted as the main mechanism involved in neurologic complications of infective endocarditis. The pathophysiology may imply other phenomena, including vasculitis. We aimed to define the cerebral lesion spectrum in an infective endocarditis rat model., Design: Experimental model of Staphylococcus aureus or Enterococcus faecalis infective endocarditis. Neurologic lesions observed in the infective endocarditis model were compared with three other conditions, namely bacteremia, nonbacterial thrombotic endocarditis, and healthy controls., Setting: Research laboratory of a university hospital., Subjects: Male Wistar rats., Interventions: Brain MRI, neuropathology, immunohistochemistry for astrocyte and microglia, and bacterial studies on brain tissue were used to characterize neurologic lesions., Measurements and Main Results: In the infective endocarditis group, MRI revealed at least one cerebral lesion in 12 of 23 rats (52%), including brain infarctions (n = 9/23, 39%) and cerebral microbleeds (n = 8/23, 35%). In the infective endocarditis group, neuropathology revealed brain infarctions (n = 12/23, 52%), microhemorrhages (n = 10/23, 44%), and inflammatory processes (i.e., cell infiltrates including abscesses, vasculitis, meningoencephalitis, and/or ependymitis; n = 11/23, 48%). In the bacteremia group, MRI studies were normal and neuropathology revealed only hemorrhages (n = 2/11, 18%). Neuropathologic patterns observed in the nonbacterial thrombotic endocarditis group were similar to those observed in the infective endocarditis group. Immunochemistry revealed higher microglial activation in the infective endocarditis group (n = 11/23, 48%), when compared with the bacteremia (n = 1/11, 9%; p = 0.03) and nonbacterial thrombotic endocarditis groups (n = 0/7, 0%; p = 0.02)., Conclusions: This original model of infective endocarditis recapitulates the neurologic lesion spectrum observed in humans and suggests synergistic mechanisms involved, including thromboembolism and cerebral vasculitis, promoted by a systemic bacteremia-mediated inflammation.

Staphylococcus aureus is able to disseminate from vascular device biofilms to the blood and organs, resulting in life-threatening infections such as endocarditis. The mechanisms behind spreading are largely unknown, especially how the bacterium escapes immune effectors and antibiotics in the process. Using an in vitro catheter infection model, we studied S. aureus biofilm growth, late-stage dispersal, and reattachment to downstream endothelial cell layers. The ability of the released biofilm material to resist host response and disseminate in vivo was furthermore studied in whole blood and phagocyte survival assays and in a short-term murine infection model. We found that S. aureus biofilms formed in flow of human plasma release biofilm thromboemboli with embedded bacteria and bacteria-secreted polysaccharides. The emboli disseminate as antibiotic and immune resistant vehicles that hold the ability to adhere to and initiate colonisation of endothelial cell layers under flow. In vivo experiments showed that the released biofilm material reached the heart similarly as ordinary broth-grown bacteria but also that clumps to some extend were trapped in the lungs. The clumping dispersal of S. aureus from in vivo-like vascular biofilms and their specific properties demonstrated here help explain the pathophysiology associated with S. aureus bloodstream infections., (© 2017 John Wiley & Sons Ltd.)

We report a case of renal embolism as an initial manifestation of Streptococcus dysgalactiae subspecies equisimilis (SDSE) endocarditis in a patient with chronic aortic dissection. A 37-year-old man who underwent total aortic arch replacement owing to aortic dissection, presented with a 3-h history of fever, chills, and acute right-sided flank pain. The endocarditis affected the native aortic valve and was complicated by a renal embolism. Blood culture results were positive for SDSE. Intravenous penicillin resulted in satisfactory clinical and echocardiographic recovery.

A 12-year-old Japanese girl developed infective endocarditis and central nervous system disease. The previously healthy girl showed altered consciousness and abnormal behaviors along with the classical signs of septic emboli. Staphylococcus aureus was isolated from peripheral blood, but not, the pleocytotic cerebrospinal fluid. Diagnostic imaging studies revealed a vegetative structure in the morphologically normal heart, and multiple thromboembolisms in the brain and spleen. Low plasma activity of protein S (12%) and thrombophilic family history allowed the genetic study, demonstrating that she carried a heterozygous mutation of PROS1 (exon 13; 1689C > T, p.R474C). Surgical intervention of the thrombotic fibrous organization and subsequent anticoagulant therapy successfully managed the disease. There are no reports of infective endocarditis in childhood occurring as the first presentation of heritable thrombophilia. Protein S deficiency might be a risk factor for the development or exacerbation of infective endocarditis in children having no pre-existing heart disease., (Copyright © 2013 Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Sources of arterial embolism range from the common, such as cardiac pathology, to less common causes. We present a case of an acutely ischaemic lower limb due to septic emboli from Staphylococcus aureus pneumonia.

The fastidious Gram-positive cocci Granulicatella adiacens, previously known as nutritionally variant streptococci (NVS) are unusual but significant cause of endocarditis due to increased mortality and morbidity. Difficulties in reaching correct bacteriological identification, increased resistance to beta-lactam antibiotics and macrolides and complicated clinical course have contributed to problems in management of cases of infective endocarditis caused by this bacterium. We present the first Indian case of endocarditis with arterial embolus by G. adiacens in an elderly male with no preexisting cardiac abnormality.

An immunocompromised patient presented with febrile episodes, an erysipelas-like rash, and thromboembolic complications. Amplification of 16S rRNA gene sequences from blood and sequence analysis revealed "Candidatus Neoehrlichia mikurensis." We report the first case of human disease caused by "Ca. Neoehrlichia mikurensis."

Background: Previous studies have reported a 12% incidence of venous thromboembolic events (VTEs) in lung transplant recipients (LTRs). Characterization of risk factors for VTEs in LTRs is lacking. We identified the incidence and risk factors associated with post-transplant VTEs., Methods: A retrospective review of 153 LTRs from 1994 to 2006 was performed. Patients were categorized by age, race, gender, weight, underlying diagnosis, procedure, ischemic time, length of stay (LOS), cardiopulmonary bypass (CPB), location and number of VTEs, mobility, immunosuppression, renal, hepatic, hematologic and coagulation profiles and nutritional status., Results: A single VTE occurred in 29% of LTRs within the study period. Fifty-eight percent had multiple VTEs and 7% had a radiologically confirmed pulmonary embolism. Median time from transplant to first VTE was 69 days. Sixty percent of VTEs occurred within 1 year, 20% of which occurred within the first month, 19% between 2 and 5 years, and 13% at beyond 5 years post-transplant. Seventy-six percent of VTEs occurred during hospitalization, 19% during outpatient status. Forty-eight percent were of the upper extremity and 47% were of the lower extremity. Sixty-one percent of LTRs were taking cyclosporine and 39% tacrolimus. VTE and non-VTE groups were similar in age, weight, body mass index (BMI), ischemic time, procedure or underlying diagnosis precipitating the need for transplant. Univariate analysis revealed LOS and CPB as significant predictors of a single VTE (p = 0.036, hazard ratio [HR] 1.006 and p = 0.045, HR 1.91, respectively). Multivariate analysis revealed only CPB as a significant predictor (p = 0.047, HR 1.929)., Conclusions: Analysis of a cohort of LTRs for a median period of 1.5 years revealed a VTE incidence much higher than previously reported, especially within the first month after transplantation.

Background: Due to the increasing number of intravenous drug users, subjects with immune deficiencies or with prosthetic valves, infective endocarditis (IE) continues to be prevalent and to have a high mortality., Aim: To review all cases of infective endocarditis diagnosed in an Internal Medicine Service., Material and Methods: Retrospective review of medical records of all patients with infective endocarditis, hospitalized in an Internal Medicine ward, between 1989 and 2003. Dukes criteria were used to define definitive, possible and less probable cases of IE., Results: Eighty seven patients with definite IE were identified (66 males, age range 19-84 years), with a mean incidence of 5.3 per 1000 hospitalizations. IE in intravenous drugs users was usually caused by Staphylococcus aureus and presented high risk of embolism (RR: 3,21). Subjects aged over 70 years had a relative risk of mortality of 5.5. Hospital acquired IE was associated with advanced age and IV catheters appeared as the only predisposing factor. Patients with prosthetic valves were also older, their main complication was abscess formation and their mortality was higher., Conclusions: A closer approach to differential conditions of patients, according to age, intravenous drug use or the presence of prosthetic valves, is necessary.

Childhood septic arthritis is not only an uncommon presentation with polyarticular involvement, but is also rarely complicated with thromboembolism. We report a case of a 10-year-old boy who suffered multiple staphylococcal arthritis, deep vein thrombosis, pulmonary embolism, pericardial effusion and occlusion of the anterior parietal branch of the right middle cerebral artery. Oxacillin-sensitive Staphylococcus aureus was isolated from blood, synovial fluid and pericardial effusion. Intravenous six-week oxacillin combined with two-week gentamicin for eradicating the pathogen, arthrotomy for debridment and subcutaneous low-molecular-weight heparin for preventing further thromboembolism were administered during admission. In addition, surveys for immunodeficiency, connective tissue disease and hemostatic dysfunction produced negative findings. The patient was discharged with neither painful disability of involved joints nor neurological sequelae.

A study of 340 necropsied dairy cattle from northern Bavaria resulted in 31 animals (9%) showing evidence of pyemic thromboembolism. The most frequent pathomorphologic lesions consisted in endocarditis valvularis thromboticans of the tricuspid and/or mitral valve (21), embolic pneumonia (26), nephritis (13) and renal infarction (12). The most common isolate found in bacteriologic culture was Arcanobacterium pyogenes in 26 of 31 cases, followed by Staphylococcus aureus (2), Mannheimia haemolytica (2) and Streptococcus bovis (1) in rare cases. In 27 of 31 cows a possible cause of pyemic thromboembolism was found; in 23 cases claw diseases and decubital ulcera were probably responsible.

Background: Lemierre's syndrome is a potentially severe though uncommon entity consisting in septic emboli from an internal jugular vein thrombus after oropharyngeal infection., Case Report: A 21-year-old man initially treated for acute pharnygeal infection developed fever and lower chest pain related to multiple pulmonary abscesses. The diagnosis of Lemierre's syndrome was retained due to the association of extensive thrombus formation in the internal jugular vein and Streptococcus intermedius septicemia., Discussion: Lemierre's syndrome is a classical entity whose frequency is probably underestimated. The causal agent is not always an anaerobic germ. Use of anticoagulants is controversial.

The authors report a clinical case of a 60-year-old Caucasian man, with two episodes of arterial embolization in the lower limbs. A microscope investigation of the emboli revealed that they originated from fungal aortitis caused by Paracoccidioides brasiliensis. A review of aortic infections showed only one similar report of this rare clinical expression of blastomycosis. The authors suggest a routine postoperative search for emboli followed by culture and histopathology.

Cardiovascular diseases, including atherosclerosis and myocardial ischemia, occur as a result of a complex set of genetic and environmental factors. During periodontitis, dental plaque microorganisms may disseminate through the blood to infect the vascular endothelium and contribute to the occurrence of atherosclerosis and risk of myocardial ischemia and infarction. Myocardial ischemia and infarction are often preceded by acute thromboembolic events. In an in vitro model of thrombosis, certain dental plaque bacteria induce platelets to aggregate. Aggregation of platelets is induced by the platelet aggregation-associated protein [PAAPJ expressed on plaque bacteria, including Streptococcus sanguis and Porphyromonas gingivalis. Intravenous infusion of S. sanguis into rabbits has been shown previously to cause changes in the electrocardiogram (ECG), heart rate, blood pressure, and cardiac contractility. These changes are consistent with the occurrence of myocardial infarction. The ECG changes are now shown to begin within 30 seconds after infusion of PAAP+ S. sanguis, followed by alterations in blood pressure and respiratory rate. These changes occurred intermittently over a 30-minute period and changed within one heartbeat to a normal pattern and suddenly back to abnormal. Intermittent ECG abnormalities were seen in 13 of 15 rabbits, including left axis deviation, ST-segment depression, preventricular contractions, alternans, and bigemnia. Dose-dependent thrombocytopenia, accumulation of 111Indium-labeled platelets in the lungs, and tachypnea also occurred. No changes occurred with the PAAp- strain. The data indicated that PAPP+ S. sanguis interacts with circulating platelets, inducing thromboemboli to cause the pulmonary and cardiac abnormalities. During periodontitis, therefore, PAAP+ S. sanguis and P. gingivalis bacteremia may contribute to the chance of acute thromboembolic events.

We describe the case of a 64-year-old woman with an iatrogenic pseudoaneurysm, arteriovenous fistula, and thrombotic occlusion of the right femoral vein with Staphylococcus aureus infection resistant to methicillin as complications of femoral catheterization for hemodialysis access. A temporary caval filter was introduced just prior to operation and kept in place for 4 days. An infected thrombus was captured and removed with a filter-catheter device. The placement of a temporary caval filter should be considered for prevention of pulmonary embolism in patients with infected venous thrombosis which requires surgical thrombectomy.

Significant medical complications after elective abortion are rare. However, complications do occur, and the emergency physician should always bear this in mind when evaluating a patient with significant illness who has recently undergone an elective abortion. Reported here is a case of postabortion endocarditis, manifesting as a septic coronary artery embolism, that led to a fatal acute myocardial infarction.

Six calves showed neurological signs with recumbency for 5 to 30 days. Histologically, they had encephalomyelitis characterized by multiple minute foci of malacia and perivascular microgliosis throughout the central nervous system. Widespread degeneration of the white matter was also detected mainly in the spinal cord. Micro-abscesses and thrombophlebitis, which were occasionally observed in the malacic lesions, suggested that the disease was a feature of infectious thrombo-embolic meningo-encephalomyelitis modified by various factors, including antibiotic therapy.

Infected thrombus in an abdominal aortic aneurysm represents a potential source of subsequent aortic graft sepsis. Previous reports have documented a 10 to 15 percent incidence of positive results of culture of the contents of an abdominal aortic aneurysm and have recommended prolonged postoperative organism-specific antibiotic therapy when a positive culture is encountered. In our study, we cultured the intraluminal thrombus during elective aneurysm repair in 64 patients with abdominal aortic aneurysms and found bacterial growth in 9 (14 percent of all patients). Eight of the nine patients received no antibiotic therapy other than the routine prophylaxis regimen, and no evidence of either early or late prosthetic graft sepsis occurred (mean follow-up 25 months). We conclude that a positive result of culture may not imply clinical infection at the time of operation and that prolonged postoperative organism-specific antibiotic therapy does not appear necessary in the patient with an asymptomatic aneurysm and no overt evidence of infection of the aneurysm at the time of operation.

Two cows affected with Haemophilus somnus were examined pathologically. Although manifested lesions were composed of fibrinopurulent meningitis without the usual parenchymatous lesions in the central nervous system, Haemophilus somnus was isolated in pure culture from the cerebral cortex of both cases. Presence of this atypical lesion in the nervous system should be kept in mind for the differential diagnosis of the disease.

Infectious thromboembolic meningoencephalitis of cattle which is caused by Haemophilus somnus has been difficult to study due, in part, to lack of model infection in a laboratory animal. Model infection was induced in 12-day-old chicken embryos after IV injection of H somnus. Death with typical lesions (hemorrhage, degeneration of brain, congestion of venules with leukocytes and meningitis) was seen in the chicken embryo between 2 and 6 days after injection of organisms. Bacteria could be demonstrated in lesions, using Warthin-Starry silver strain. Three stable colonial variants of H somnus were cultured from dead embryos. They appeared as small translucent (ST), small opaque (SO), and large opaque (LO). Lethal dose50 values of ST was 4.4 x 10(4); for SO, 3.6 x 10(4); and for LO, 8 x 10(6). Statistical analysis indicated that ST and SO were significantly more lethal (P less than 0.001) than LO.

Nine feedlot cattle showed clinical signs consistent with those expected in thromboembolic meningoencephalitis. These signs included pyrexia, ataxia, posterior paresis, paralysis and coma. Brown necrotic foci with haemorrhagic borders were observed in the brains of three animals that had died. In these foci vasculitis, thrombosis, infarction and neutrophil infiltration were observed during microscopical examination. Haemophilus somnus was isolated in pure culture from the brains.

An 8-year-old mixed-breed dog was evaluated for caudal paresis. Transient lameness of the left hind and left forelimbs had developed during the preceding week. Clinical findings included conscious proprioceptive deficits, hyporeflexive tendon reflexes and decreased pain perception, coolness in the hind limbs and left forelimb, and absence of femoral pulses. A fluid-dense mass was radiographically identified adjacent to the left atrium. Echocardiography revealed a mass in the left atrium and spontaneous contrast in the left ventricular lumen and aortic root. The dog was euthanatized because of its deteriorating condition. A large mass was adhered to the dorsal left atrial wall and had eroded into the atrial lumen. A sterile blood clot was attached to this site, and sterile thrombi were in the terminal portion of the aorta. Histologically, the mass was found to be hilar lymph node with chronic pyogranulomatous inflammation containing organisms characteristic of Blastomyces dermatitidis.

Nonimmune binding of immunoglobulin to whole bacteria was quantitated for North American isolates of Haemophilus somnus recovered from cattle with pneumonia, reproductive failure (abortion), or thromboembolic meningoencephalitis or from the vagina or prepuce of carrier cattle. Quantitative binding activity covered a wide range, with most pathogenic and carrier isolates demonstrating significant immunoglobulin-Fc binding. Isolates for which Fc binding was not detectable were recovered only from the prepuces of asymptomatic bulls. Expression of Fc-binding activity correlated with the presence of the 41,000-molecular-weight protein (41K protein) and 270K protein. Isolates that lacked Fc-binding activity did not possess 41K or 270K protein. A 33K protein was detected in isolates that lacked Fc-binding activity but not in isolates that bound Fc.

Three colony variants (translucent, small opaque, and large opaque) of Haemophilus somnus recovered during infection studies of chicken embryos were examined using electron microscopy. Ruthenium red-strained H somnus preparations revealed no capsule in any variants. Pili were not seen on phosphotungstate-negative stained preparations. The translucent variant was thin-walled and had an irregular, pleomorphic rod shape. The small opaque variant had a thicker cell wall and an even rod shape. The large opaque variant had the thickest, most rigid wall of the 3, with uniform rod morphologic features. When each of the 3 variants was allowed to contact bovine epithelial turbinate cells, the translucent and small opaque were significantly (P less than 0.01) more adherent than was the large opaque variant.