# on 12-Feb-2021 (Fri)

#### Annotation 6229433126156

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite An aneurysm is an abnormal focal arterial dilation

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opics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Dec 2020. | This topic last updated: Jul 08, 2019. INTRODUCTION — <span>An aneurysm is an abnormal focal arterial dilation. Preexisting aneurysms can become secondarily infected, but aneurysmal degeneration of the arterial wall can also be the result of infection that may be due to bacteremia or septic embo

#### Annotation 6229436271884

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite The name mycotic aneurysm was coined by Osler to describe aneurysms associated with bacterial endocarditis [1]. These were noted to have the appearance of "fresh fungus vegetations"; however, the majority of mycotic aneurysms are caused by bacteria

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ondarily infected, but aneurysmal degeneration of the arterial wall can also be the result of infection that may be due to bacteremia or septic embolization, as in the case of mycotic aneurysm. <span>The name mycotic aneurysm was coined by Osler to describe aneurysms associated with bacterial endocarditis [1]. These were noted to have the appearance of "fresh fungus vegetations"; however, the majority of mycotic aneurysms are caused by bacteria. Although some authors use the term "mycotic" to describe infected aneurysm regardless of etiology, we will limit the use of this term to those aneurysms that develop when material orig

#### Annotation 6229438893324

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Although some authors use the term "mycotic" to describe infected aneurysm regardless of etiology, we will limit the use of this term to those aneurysms that develop when material originating in the heart causes arterial wall infection and, subsequently, dilation [2]

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e aneurysms associated with bacterial endocarditis [1]. These were noted to have the appearance of "fresh fungus vegetations"; however, the majority of mycotic aneurysms are caused by bacteria. <span>Although some authors use the term "mycotic" to describe infected aneurysm regardless of etiology, we will limit the use of this term to those aneurysms that develop when material originating in the heart causes arterial wall infection and, subsequently, dilation [2]. Aneurysms are classified into true and false, or pseudoaneurysms. True aneurysms involve all three layers of the arterial wall (intima, media, and adventitia). A false, or pseudo-, ane

#### Annotation 6229441514764

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Aneurysms are classified into true and false, or pseudoaneurysms. True aneurysms involve all three layers of the arterial wall (intima, media, and adventitia). A false, or pseudo-, aneurysm is a collection of blood or hematoma that has leaked out of the artery but is then confined by the surrounding tissue

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regardless of etiology, we will limit the use of this term to those aneurysms that develop when material originating in the heart causes arterial wall infection and, subsequently, dilation [2]. <span>Aneurysms are classified into true and false, or pseudoaneurysms. True aneurysms involve all three layers of the arterial wall (intima, media, and adventitia). A false, or pseudo-, aneurysm is a collection of blood or hematoma that has leaked out of the artery but is then confined by the surrounding tissue. Infected aneurysm is a serious clinical condition that is associated with significant morbidity and mortality. Treatment consists of antibiotic therapy combined with aggressive surgica

#### Annotation 6229444136204

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Arterial injury – Arterial injury is an important risk factor for an infected aneurysm. Artery injury resulting in infected femoral artery pseudoaneurysm is commonly due to intravenous drug use (self-inflicted), but iatrogenic mechanisms, such as invasive monitoring, percutaneous access for cardiac catheterization, or other peripheral interventions, can also lead to infected aneurysm [3,4]. Arterial injury may result from other mechanisms, such as gastrointestinal perforation [5,6] or peripheral nerve block [7]. (See 'Direct bacterial inoculation' below.)

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ic reviews. (See "Iliac artery aneurysm" and "Popliteal artery aneurysm" and "Management of asymptomatic abdominal aortic aneurysm".) RISK FACTORS — Risk factors for infected aneurysm include: ●<span>Arterial injury – Arterial injury is an important risk factor for an infected aneurysm. Artery injury resulting in infected femoral artery pseudoaneurysm is commonly due to intravenous drug use (self-inflicted), but iatrogenic mechanisms, such as invasive monitoring, percutaneous access for cardiac catheterization, or other peripheral interventions, can also lead to infected aneurysm [3,4]. Arterial injury may result from other mechanisms, such as gastrointestinal perforation [5,6] or peripheral nerve block [7]. (See 'Direct bacterial inoculation' below.) ●Antecedent infection – In a retrospective review, nearly half of 43 patients with an infected aortic aneurysm were found to have an antecedent infection that included pneumonia, cholec

#### Annotation 6229446757644

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Antecedent infection – In a retrospective review, nearly half of 43 patients with an infected aortic aneurysm were found to have an antecedent infection that included pneumonia, cholecystitis, urinary tract infection, endocarditis, diverticulitis, soft tissue infection, and osteomyelitis. In the pre-antibiotic era, the majority of infected aneurysms were due to endocarditis. More contemporary series identify endocarditis as the likely etiology in 17 to 29 percent of cases [8,9]. The rapid development of an infected aortic aneurysm associated with periodontal infection and oral surgery has also been reported [10-13]. (See 'Septic emboli (mycotic aneurysm)' below.)

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infected aneurysm [3,4]. Arterial injury may result from other mechanisms, such as gastrointestinal perforation [5,6] or peripheral nerve block [7]. (See 'Direct bacterial inoculation' below.) ●<span>Antecedent infection – In a retrospective review, nearly half of 43 patients with an infected aortic aneurysm were found to have an antecedent infection that included pneumonia, cholecystitis, urinary tract infection, endocarditis, diverticulitis, soft tissue infection, and osteomyelitis. In the pre-antibiotic era, the majority of infected aneurysms were due to endocarditis. More contemporary series identify endocarditis as the likely etiology in 17 to 29 percent of cases [8,9]. The rapid development of an infected aortic aneurysm associated with periodontal infection and oral surgery has also been reported [10-13]. (See 'Septic emboli (mycotic aneurysm)' below.) ●Impaired immunity – Immunosuppressive states predispose the patient to infection, which may present with atypical clinical features. Immunosuppressive disorders were found in 70 percen

#### Annotation 6229449379084

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Impaired immunity – Immunosuppressive states predispose the patient to infection, which may present with atypical clinical features. Immunosuppressive disorders were found in 70 percent of patients with infected aneurysms in a review of 43 patients [14]. Diabetes, alcoholism, chronic glucocorticoid therapy, chemotherapy, and malignancy have been identified as possible risk factors for infected aneurysm [14-18]. Immune mechanisms may play a role in the development of infected aneurysm in a variety of other circumstances, such as in patients with cancer [19], cirrhosis [20], those undergoing hemodialysis [21], following gastrointestinal endoscopy [22], posttransplant, those with HIV infection [23-25], and following trauma or near drowning [26]. (See 'Bacteremic seeding' below.)

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,9]. The rapid development of an infected aortic aneurysm associated with periodontal infection and oral surgery has also been reported [10-13]. (See 'Septic emboli (mycotic aneurysm)' below.) ●<span>Impaired immunity – Immunosuppressive states predispose the patient to infection, which may present with atypical clinical features. Immunosuppressive disorders were found in 70 percent of patients with infected aneurysms in a review of 43 patients [14]. Diabetes, alcoholism, chronic glucocorticoid therapy, chemotherapy, and malignancy have been identified as possible risk factors for infected aneurysm [14-18]. Immune mechanisms may play a role in the development of infected aneurysm in a variety of other circumstances, such as in patients with cancer [19], cirrhosis [20], those undergoing hemodialysis [21], following gastrointestinal endoscopy [22], posttransplant, those with HIV infection [23-25], and following trauma or near drowning [26]. (See 'Bacteremic seeding' below.) ●Atherosclerosis – Patients with atherosclerosis, particularly older adults, are at risk for bacteremic seeding of atheromatous plaques. (See 'Bacteremic seeding' below.) ●Preexisting a

#### Annotation 6229452000524

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Atherosclerosis – Patients with atherosclerosis, particularly older adults, are at risk for bacteremic seeding of atheromatous plaques. (See 'Bacteremic seeding' below.)

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ng hemodialysis [21], following gastrointestinal endoscopy [22], posttransplant, those with HIV infection [23-25], and following trauma or near drowning [26]. (See 'Bacteremic seeding' below.) ●<span>Atherosclerosis – Patients with atherosclerosis, particularly older adults, are at risk for bacteremic seeding of atheromatous plaques. (See 'Bacteremic seeding' below.) ●Preexisting aneurysm – Preexisting aneurysms are at risk for secondary infection due to bacteremia or spread from a contiguous infection. The prevalence of infection in a preexisting a

#### Annotation 6229454621964

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Preexisting aneurysm – Preexisting aneurysms are at risk for secondary infection due to bacteremia or spread from a contiguous infection. The prevalence of infection in a preexisting aneurysm is low. In a study that cultured aortic tissue from patients undergoing elective aneurysm repair, positive cultures were obtained in 33 of 88 patients [27]. Positive cultures were associated with subsequent infected grafts in three patients. However, the majority of patients with positive aortic cultures had no known negative sequelae

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emic seeding' below.) ●Atherosclerosis – Patients with atherosclerosis, particularly older adults, are at risk for bacteremic seeding of atheromatous plaques. (See 'Bacteremic seeding' below.) ●<span>Preexisting aneurysm – Preexisting aneurysms are at risk for secondary infection due to bacteremia or spread from a contiguous infection. The prevalence of infection in a preexisting aneurysm is low. In a study that cultured aortic tissue from patients undergoing elective aneurysm repair, positive cultures were obtained in 33 of 88 patients [27]. Positive cultures were associated with subsequent infected grafts in three patients. However, the majority of patients with positive aortic cultures had no known negative sequelae. (See 'Bacteremic seeding' below and 'Contiguous infection' below.) ETIOLOGY Direct bacterial inoculation — Direct inoculation of bacteria into the arterial wall can occur at the time o

#### Annotation 6229457243404

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Direct bacterial inoculation — Direct inoculation of bacteria into the arterial wall can occur at the time of vascular injury. An arterial injury may be self-inflicted, iatrogenic, accidental, or due to assault (gunshot, stab). Infected pseudoaneurysm following arterial injury has become one of the most common forms of infected aneurysm. The femoral artery is the most commonly involved arterial site.

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ts in three patients. However, the majority of patients with positive aortic cultures had no known negative sequelae. (See 'Bacteremic seeding' below and 'Contiguous infection' below.) ETIOLOGY <span>Direct bacterial inoculation — Direct inoculation of bacteria into the arterial wall can occur at the time of vascular injury. An arterial injury may be self-inflicted, iatrogenic, accidental, or due to assault (gunshot, stab). Infected pseudoaneurysm following arterial injury has become one of the most common forms of infected aneurysm. The femoral artery is the most commonly involved arterial site. Self-induced infected pseudoaneurysms are the result of injection drug abuse wherein users inadvertently inoculate themselves via contaminated needles into the arterial wall (they are a

#### Annotation 6229459864844

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Bacteremic seeding — Bacteremic seeding of an existing intimal injury, atherosclerotic plaque, or preexisting aneurysm can lead to arterial wall infection. The intima is normally highly resistant to infection, but, when diseased, it allows bacteria to pass through it into deeper layers of the arterial wall. Once a local infection is established, suppuration, localized perforation, and pseudoaneurysm can result. The aorta is the most common location affected primarily since it is the most frequent site of atherosclerosis, but peripheral arteries can also be affected. Infected aneurysm can occur in the absence of significant atherosclerosis [28]. In a similar manner, preexisting aneurysms may become secondarily infected, which may predispose to rupture. In a study of 80 patients undergoing open aortic repair, a greater number of positive cultures were found in patients with ruptured aneurysms compared with asymptomatic and symptomatic aneurysms (38 versus 9 and 13 percent, respectively) [29].

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urrounding hematoma. Infected pseudoaneurysms of the common femoral artery are most common, but infection involving the external iliac, carotid, and subclavian arteries have also been reported. <span>Bacteremic seeding — Bacteremic seeding of an existing intimal injury, atherosclerotic plaque, or preexisting aneurysm can lead to arterial wall infection. The intima is normally highly resistant to infection, but, when diseased, it allows bacteria to pass through it into deeper layers of the arterial wall. Once a local infection is established, suppuration, localized perforation, and pseudoaneurysm can result. The aorta is the most common location affected primarily since it is the most frequent site of atherosclerosis, but peripheral arteries can also be affected. Infected aneurysm can occur in the absence of significant atherosclerosis [28]. In a similar manner, preexisting aneurysms may become secondarily infected, which may predispose to rupture. In a study of 80 patients undergoing open aortic repair, a greater number of positive cultures were found in patients with ruptured aneurysms compared with asymptomatic and symptomatic aneurysms (38 versus 9 and 13 percent, respectively) [29]. Rupture of abdominal aortic aneurysms is discussed elsewhere. (See "Management of symptomatic (non-ruptured) and ruptured abdominal aortic aneurysm", section on 'Introduction'.) Contigu

#### Annotation 6229462486284

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Contiguous infection — A focus of infection can extend to the arterial wall. Extension of a postoperative infection can lead to an infected aneurysm and has been described in the setting of appendectomy [30], cholecystectomy [31], colorectal surgery [32,33], as a result of pancreatic pseudocyst [34], and following knee or hip replacement surgery [35-37]. Extension of infection not related to surgery can also occur as seen in vertebral osteomyelitis [38-40]

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ectively) [29]. Rupture of abdominal aortic aneurysms is discussed elsewhere. (See "Management of symptomatic (non-ruptured) and ruptured abdominal aortic aneurysm", section on 'Introduction'.) <span>Contiguous infection — A focus of infection can extend to the arterial wall. Extension of a postoperative infection can lead to an infected aneurysm and has been described in the setting of appendectomy [30], cholecystectomy [31], colorectal surgery [32,33], as a result of pancreatic pseudocyst [34], and following knee or hip replacement surgery [35-37]. Extension of infection not related to surgery can also occur as seen in vertebral osteomyelitis [38-40]. Septic emboli (mycotic aneurysm) — Septic embolic from the heart can occlude the vasa vasorum of the vessel or the vessel lumen, leading to vascular wall infection and mycotic aneurysm

#### Annotation 6229465107724

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Septic emboli (mycotic aneurysm) — Septic embolic from the heart can occlude the vasa vasorum of the vessel or the vessel lumen, leading to vascular wall infection and mycotic aneurysm formation. Embolism is estimated to occur in between 25 and 50 percent of patients, but only about 1 to 5 percent develop symptomatic mycotic aneurysm [41]. Because of their embolic nature, mycotic aneurysms tend to be multiple, but they can also be solitary [42]. Spontaneous resolution with antibiotic therapy for endocarditis has been reported [43-45]. As such, the true prevalence of mycotic aneurysm is unknown

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lt of pancreatic pseudocyst [34], and following knee or hip replacement surgery [35-37]. Extension of infection not related to surgery can also occur as seen in vertebral osteomyelitis [38-40]. <span>Septic emboli (mycotic aneurysm) — Septic embolic from the heart can occlude the vasa vasorum of the vessel or the vessel lumen, leading to vascular wall infection and mycotic aneurysm formation. Embolism is estimated to occur in between 25 and 50 percent of patients, but only about 1 to 5 percent develop symptomatic mycotic aneurysm [41]. Because of their embolic nature, mycotic aneurysms tend to be multiple, but they can also be solitary [42]. Spontaneous resolution with antibiotic therapy for endocarditis has been reported [43-45]. As such, the true prevalence of mycotic aneurysm is unknown. Mycotic aneurysms can develop anywhere but are most commonly seen in the intracranial arteries, followed by visceral arteries and upper or lower extremity arteries, typically occurring

#### Annotation 6229470350604

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Blood cultures are positive in 50 to 85 percent of cases [48,49]. Organisms have been isolated from aneurysmal tissue in up to 76 percent of patients [29,48]. In one case series, multiple organisms were isolated in 8 percent, and no pathogen was identified in 25 percent of cases [8]. Identification of the causative organism using molecular methods (bacterial 16S ribosomal RNA) has been described [50]

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t were extracranial [42]. Six peripheral artery aneurysms were identified; two in popliteal and one each in the ulnar artery, humeral artery, hepatic artery, and coronary artery. MICROBIOLOGY — <span>Blood cultures are positive in 50 to 85 percent of cases [48,49]. Organisms have been isolated from aneurysmal tissue in up to 76 percent of patients [29,48]. In one case series, multiple organisms were isolated in 8 percent, and no pathogen was identified in 25 percent of cases [8]. Identification of the causative organism using molecular methods (bacterial 16S ribosomal RNA) has been described [50]. Although bacteriologic patterns continue to evolve over time, the organisms with the greatest affinity for the arterial wall, Staphylococcus spp and Salmonella spp, remain the most com

#### Annotation 6229472972044

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Although bacteriologic patterns continue to evolve over time, the organisms with the greatest affinity for the arterial wall, Staphylococcus spp and Salmonella spp, remain the most common [51-53]. Staphylococcus aureus is the most common pathogen reported in 28 to 71 percent of cases [8,48]

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in 8 percent, and no pathogen was identified in 25 percent of cases [8]. Identification of the causative organism using molecular methods (bacterial 16S ribosomal RNA) has been described [50]. <span>Although bacteriologic patterns continue to evolve over time, the organisms with the greatest affinity for the arterial wall, Staphylococcus spp and Salmonella spp, remain the most common [51-53]. Staphylococcus aureus is the most common pathogen reported in 28 to 71 percent of cases [8,48]. In several reports of infected aneurysms, methicillin-resistant S. aureus (MRSA) predominates [54-56]. In one series of preexisting aneurysms, Staphylococcus epidermidis was the most p

#### Annotation 6229475593484

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Salmonella is reported in 15 to 24 percent of cases [8,51]. The diseased aorta appears to be vulnerable to Salmonella, and this pathogen is frequently isolated in infected aneurysms due to bacteremic seeding of atherosclerotic plaque [58].

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series of preexisting aneurysms, Staphylococcus epidermidis was the most prevalent organism [29]. Infected aneurysm due to vancomycin-intermediate S. aureus (VISA) has also been described [57]. <span>Salmonella is reported in 15 to 24 percent of cases [8,51]. The diseased aorta appears to be vulnerable to Salmonella, and this pathogen is frequently isolated in infected aneurysms due to bacteremic seeding of atherosclerotic plaque [58]. Streptococcus pneumoniae was a frequent etiology of infected aneurysms in the pre-antibiotic era but became rare with the advent of penicillin; however, S. pneumoniae may be reemerging

#### Annotation 6229478214924

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Streptococcus pneumoniae was a frequent etiology of infected aneurysms in the pre-antibiotic era but became rare with the advent of penicillin; however, S. pneumoniae may be reemerging as a cause of infected aneurysms [59,60].

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cases [8,51]. The diseased aorta appears to be vulnerable to Salmonella, and this pathogen is frequently isolated in infected aneurysms due to bacteremic seeding of atherosclerotic plaque [58]. <span>Streptococcus pneumoniae was a frequent etiology of infected aneurysms in the pre-antibiotic era but became rare with the advent of penicillin; however, S. pneumoniae may be reemerging as a cause of infected aneurysms [59,60]. Other gram-negative organisms are also associated with bacteremic seeding [32,61-63]. In one study, although gram-positive organisms predominated, gram-negative organisms were seen in 3

#### Annotation 6229480836364

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Other gram-negative organisms are also associated with bacteremic seeding [32,61-63]. In one study, although gram-positive organisms predominated, gram-negative organisms were seen in 35 percent of cases [63]. In this study, gram-negative infections were associated with a higher incidence of aneurysm rupture (84 versus 10 percent) and mortality (84 versus 50 percent) compared with gram-positive organisms.

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equent etiology of infected aneurysms in the pre-antibiotic era but became rare with the advent of penicillin; however, S. pneumoniae may be reemerging as a cause of infected aneurysms [59,60]. <span>Other gram-negative organisms are also associated with bacteremic seeding [32,61-63]. In one study, although gram-positive organisms predominated, gram-negative organisms were seen in 35 percent of cases [63]. In this study, gram-negative infections were associated with a higher incidence of aneurysm rupture (84 versus 10 percent) and mortality (84 versus 50 percent) compared with gram-positive organisms. Less common causes of infected aneurysm include Treponema pallidum and Mycobacterium spp including Mycobacterium bovis BCG [64-68]. Syphilis (T. pallidum) once caused up to 50 percent o

#### Annotation 6229483457804

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Less common causes of infected aneurysm include Treponema pallidum and Mycobacterium spp including Mycobacterium bovis BCG [64-68]. Syphilis (T. pallidum) once caused up to 50 percent of infected aneurysms (image 1). Tuberculosis is a rare cause of infected aneurysms and is most often due to erosion of periaortic lymph nodes into the aortic wall. One review of cases of infected aneurysm caused by Mycobacterium tuberculosis found only 41 cases between 1945 and 1999 [69].

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is study, gram-negative infections were associated with a higher incidence of aneurysm rupture (84 versus 10 percent) and mortality (84 versus 50 percent) compared with gram-positive organisms. <span>Less common causes of infected aneurysm include Treponema pallidum and Mycobacterium spp including Mycobacterium bovis BCG [64-68]. Syphilis (T. pallidum) once caused up to 50 percent of infected aneurysms (image 1). Tuberculosis is a rare cause of infected aneurysms and is most often due to erosion of periaortic lymph nodes into the aortic wall. One review of cases of infected aneurysm caused by Mycobacterium tuberculosis found only 41 cases between 1945 and 1999 [69]. Coxiella burnetii can also be the cause of an infected aneurysm [70-74]. A C. burnetii–infected aneurysm can occur without other manifestations of chronic Q fever [70]. Fungal arterial

#### Annotation 6229486079244

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Coxiella burnetii can also be the cause of an infected aneurysm [70-74]. A C. burnetii–infected aneurysm can occur without other manifestations of chronic Q fever [70].

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ften due to erosion of periaortic lymph nodes into the aortic wall. One review of cases of infected aneurysm caused by Mycobacterium tuberculosis found only 41 cases between 1945 and 1999 [69]. <span>Coxiella burnetii can also be the cause of an infected aneurysm [70-74]. A C. burnetii–infected aneurysm can occur without other manifestations of chronic Q fever [70]. Fungal arterial infections are also rare but may occur in patients with immune suppression, diabetes mellitus, or following treatment of a disseminated fungal disease. Pathogens include

#### Annotation 6229488700684

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Fungal arterial infections are also rare but may occur in patients with immune suppression, diabetes mellitus, or following treatment of a disseminated fungal disease. Pathogens include Candida [75], Cryptococcus [76], Aspergillus [77], Pseudallescheria boydii [26], and Scedosporium apiospermum [78].

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ween 1945 and 1999 [69]. Coxiella burnetii can also be the cause of an infected aneurysm [70-74]. A C. burnetii–infected aneurysm can occur without other manifestations of chronic Q fever [70]. <span>Fungal arterial infections are also rare but may occur in patients with immune suppression, diabetes mellitus, or following treatment of a disseminated fungal disease. Pathogens include Candida [75], Cryptococcus [76], Aspergillus [77], Pseudallescheria boydii [26], and Scedosporium apiospermum [78]. Many other organisms have also been reported to cause infected aneurysms, including: ●Other gram-positive organisms (eg, non-pneumococcal Streptococcus [79], Clostridium [80], Corynebac

#### Annotation 6229747698956

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite The classic presentation of an infected aneurysm is a painful, pulsatile, and enlarging mass together with systemic features of infection, such as fever. This presentation is more likely to be found for infected aneurysms that are superficial in location (eg, common femoral artery). In one series of 52 infected aneurysms among intravenous drug users, a tender indurated mass was palpated in 92 percent of cases; these were pulsatile in 52 percent of cases [48]. A bruit was heard in 50 percent of cases, fever was observed in 48 percent, and there was bleeding at the injection site in 15 percent of cases

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[95], Burkholderia pseudomallei [melioidosis] [96-100]) and Campylobacter [101,102] ●Anaerobes (eg, Bacteroides [103]), Eikenella [104], and Clostridium septicum [105] CLINICAL MANIFESTATIONS — <span>The classic presentation of an infected aneurysm is a painful, pulsatile, and enlarging mass together with systemic features of infection, such as fever. This presentation is more likely to be found for infected aneurysms that are superficial in location (eg, common femoral artery). In one series of 52 infected aneurysms among intravenous drug users, a tender indurated mass was palpated in 92 percent of cases; these were pulsatile in 52 percent of cases [48]. A bruit was heard in 50 percent of cases, fever was observed in 48 percent, and there was bleeding at the injection site in 15 percent of cases. In some cases, infected aneurysm may be masked by overlying inflammation. Thus, the presence of a soft tissue infection in association with a major blood vessel should raise suspicion

#### Annotation 6229752941836

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Infected aneurysms involving the aorta or iliac arteries may be accompanied by abdominal or back pain. On the other hand, patients with infected aortic aneurysm may manifest only with fever of unknown origin, some of whom will remain undiagnosed until rupture.

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eurysm. Infected aneurysm can be easily misdiagnosed as cellulitis, abscess, or thrombophlebitis. For deeper sites, the aneurysm may not be palpable and may be apparent only on imaging studies. <span>Infected aneurysms involving the aorta or iliac arteries may be accompanied by abdominal or back pain. On the other hand, patients with infected aortic aneurysm may manifest only with fever of unknown origin, some of whom will remain undiagnosed until rupture. (See "Clinical features and diagnosis of abdominal aortic aneurysm".) Infected aortic aneurysm must be distinguished from inflammatory aortic aneurysm, which can have similar clinical f

#### Annotation 6229755563276

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Inflammatory aneurysms are characterized by an inflammatory infiltrate in the aortic adventitia associated with adventitial fibrosis. Diagnostic signs on abdominal computed tomography (CT) help to differentiate these

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hed from inflammatory aortic aneurysm, which can have similar clinical features, such as fever, weight loss, nonspecific abdominal pain, and elevated erythrocyte sedimentation rate (ESR) [106]. <span>Inflammatory aneurysms are characterized by an inflammatory infiltrate in the aortic adventitia associated with adventitial fibrosis. Diagnostic signs on abdominal computed tomography (CT) help to differentiate these. (See 'Infected versus inflammatory aneurysm' below.) Infected aneurysm of the intracerebral vessels may present as stroke or subarachnoid hemorrhage, particularly in the setting of end

#### Annotation 6229760806156

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite The diagnosis of an infected aneurysm is based upon imaging the aneurysm, and infection is confirmed by culturing an organism from the blood. Computed tomographic (CT) angiography definitively diagnoses the aneurysm, specific features suggest infection, and CT also simultaneously evaluates the status of the circulation [117]

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f lower extremity peripheral nerve syndromes".) DIAGNOSIS — Suspicion of an infected aneurysm based upon history and physical findings should be followed up with laboratory and imaging studies. <span>The diagnosis of an infected aneurysm is based upon imaging the aneurysm, and infection is confirmed by culturing an organism from the blood. Computed tomographic (CT) angiography definitively diagnoses the aneurysm, specific features suggest infection, and CT also simultaneously evaluates the status of the circulation [117]. (See 'Imaging' below.) On laboratory examination, an increased white blood cell count is found in 64 to 71 percent of patients [51,118,119]. Inflammatory markers, including C-reactive

#### Annotation 6229763427596

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite On laboratory examination, an increased white blood cell count is found in 64 to 71 percent of patients [51,118,119]. Inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), are generally elevated. Blood cultures (aerobic, anaerobic, fungal) should be obtained in any patient with a suspected infected aneurysm. Because blood culture may be negative in 25 to 50 percent of patients, negative blood cultures alone are not sufficient to rule out infected aneurysm.

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aphic (CT) angiography definitively diagnoses the aneurysm, specific features suggest infection, and CT also simultaneously evaluates the status of the circulation [117]. (See 'Imaging' below.) <span>On laboratory examination, an increased white blood cell count is found in 64 to 71 percent of patients [51,118,119]. Inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), are generally elevated. Blood cultures (aerobic, anaerobic, fungal) should be obtained in any patient with a suspected infected aneurysm. Because blood culture may be negative in 25 to 50 percent of patients, negative blood cultures alone are not sufficient to rule out infected aneurysm. An infected aneurysm may be first suspected in the operating room based upon purulence in association with a preexisting aneurysm [120]. Tissue samples of the aneurysm wall should be se

#### Annotation 6229766049036

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite An infected aneurysm may be first suspected in the operating room based upon purulence in association with a preexisting aneurysm [120]. Tissue samples of the aneurysm wall should be sent for culture (aerobic, anaerobic, fungal) and Gram stain. In the operating room, a negative Gram stain is not sufficient to exclude a diagnosis of infected aneurysm [118]. Conversely, positive tissue cultures in the absence of clinical findings do not confirm an infected aneurysm in the absence of appropriate clinical findings. In one study, 69 percent of patients had positive preoperative blood cultures and 92 percent had positive aneurysm wall cultures, but the operative Gram stain was positive in only 50 percent of patients with ruptured infected aneurysms and 11 percent of unruptured but infected aneurysms [118].

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atient with a suspected infected aneurysm. Because blood culture may be negative in 25 to 50 percent of patients, negative blood cultures alone are not sufficient to rule out infected aneurysm. <span>An infected aneurysm may be first suspected in the operating room based upon purulence in association with a preexisting aneurysm [120]. Tissue samples of the aneurysm wall should be sent for culture (aerobic, anaerobic, fungal) and Gram stain. In the operating room, a negative Gram stain is not sufficient to exclude a diagnosis of infected aneurysm [118]. Conversely, positive tissue cultures in the absence of clinical findings do not confirm an infected aneurysm in the absence of appropriate clinical findings. In one study, 69 percent of patients had positive preoperative blood cultures and 92 percent had positive aneurysm wall cultures, but the operative Gram stain was positive in only 50 percent of patients with ruptured infected aneurysms and 11 percent of unruptured but infected aneurysms [118]. Imaging — Imaging studies for detection of intracranial mycotic aneurysm include CT angiography, magnetic resonance (MR) angiography, and digital subtraction angiography (DSA) [41]. Of

#### Annotation 6229771291916

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Findings on CT angiography suggestive of an infected aneurysm include the following [121,123-127] : ● Saccular, eccentric aneurysm or multilobulated aneurysm ● Soft tissue inflammation or mass around a vessel ● Aneurysm with intramural air or air collection around the vessel ● Perivascular fluid collection

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sculature to identify multifocal disease. In the setting of high clinical suspicion for intracranial mycotic aneurysm with negative imaging results, conventional angiography is reasonable [41]. <span>Findings on CT angiography suggestive of an infected aneurysm include the following [121,123-127] : ●Saccular, eccentric aneurysm or multilobulated aneurysm ●Soft tissue inflammation or mass around a vessel ●Aneurysm with intramural air or air collection around the vessel ●Perivascular fluid collection In the mesenteric circulation, indistinct fat planes may be indicative of vascular inflammation [128,129]. If a diagnosis of infected aneurysm remains in doubt, a repeat scan can be per

#### Annotation 6229776534796

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Nuclear medicine studies, including fluorodeoxyglucose–positron emission tomography (FDG-PET) and gallium scanning, are alternative modalities for evaluating infected aneurysm [130-136]. The use of FDG-PET/CT in the diagnosis of infected aneurysms has been described in case series [71,137].

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features and diagnosis of abdominal aortic aneurysm", section on 'Diagnosis'.) DSA is not reliable for identifying infected aneurysm; DSA is also invasive and associated with potential hazards. <span>Nuclear medicine studies, including fluorodeoxyglucose–positron emission tomography (FDG-PET) and gallium scanning, are alternative modalities for evaluating infected aneurysm [130-136]. The use of FDG-PET/CT in the diagnosis of infected aneurysms has been described in case series [71,137]. Imaging studies for detection of extracranial mycotic aneurysm include CT or multislice CT angiography with 3D reconstruction. Transesophageal echocardiography (TEE) is useful for ident

#### Annotation 6229781777676

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Infected versus inflammatory aneurysm — An inflammatory aneurysm is defined as an aneurysm with a ≥1 cm thickness inflammatory rind surrounding the aorta on CT. The periaortic soft tissue density sometimes enhances with intravenous contrast and the ureters may be deviated medially [106]. Periaortic fibrosis associated with inflammatory aneurysm may result in adhesion of adjacent structures, such as the ureters and duodenum to aorta, leading to indistinct retroperitoneal tissue planes on imaging studies. Inflammatory aneurysms are not associated with periaortic air or fluid and are not infected.

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clude CT or multislice CT angiography with 3D reconstruction. Transesophageal echocardiography (TEE) is useful for identifying mycotic aneurysm of the sinus of Valsalva and thoracic aorta [41]. <span>Infected versus inflammatory aneurysm — An inflammatory aneurysm is defined as an aneurysm with a ≥1 cm thickness inflammatory rind surrounding the aorta on CT. The periaortic soft tissue density sometimes enhances with intravenous contrast and the ureters may be deviated medially [106]. Periaortic fibrosis associated with inflammatory aneurysm may result in adhesion of adjacent structures, such as the ureters and duodenum to aorta, leading to indistinct retroperitoneal tissue planes on imaging studies. Inflammatory aneurysms are not associated with periaortic air or fluid and are not infected. (See "Clinical features and diagnosis of abdominal aortic aneurysm", section on 'Infected versus inflammatory AAA'.) MANAGEMENT — There are no randomized trials to guide the management

#### Annotation 6229784399116

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite There are no randomized trials to guide the management of infected aneurysms. Management strategies are primarily based upon clinical experience guided by case series.

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t associated with periaortic air or fluid and are not infected. (See "Clinical features and diagnosis of abdominal aortic aneurysm", section on 'Infected versus inflammatory AAA'.) MANAGEMENT — <span>There are no randomized trials to guide the management of infected aneurysms. Management strategies are primarily based upon clinical experience guided by case series. The standard treatment of most infected aneurysms is antibiotic therapy combined with surgical debridement with or without revascularization [118]. Revascularization procedures are perf

#### Annotation 6229787020556

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite The standard treatment of most infected aneurysms is antibiotic therapy combined with surgical debridement with or without revascularization [118]. Revascularization procedures are performed, as needed, depending upon the affected vascular bed and status of distal perfusion. For patients who refuse surgery or who have significant medical comorbidities that preclude surgical intervention, antibiotic therapy alone is an option.

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atory AAA'.) MANAGEMENT — There are no randomized trials to guide the management of infected aneurysms. Management strategies are primarily based upon clinical experience guided by case series. <span>The standard treatment of most infected aneurysms is antibiotic therapy combined with surgical debridement with or without revascularization [118]. Revascularization procedures are performed, as needed, depending upon the affected vascular bed and status of distal perfusion. For patients who refuse surgery or who have significant medical comorbidities that preclude surgical intervention, antibiotic therapy alone is an option. Endovascular techniques are emerging as a treatment alternative for infected aneurysm, most commonly for infected aortic aneurysms [117,138-149]. (See 'Role of endovascular techniques'

#### Annotation 6229789641996

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Antibiotic therapy — The initial choice of antibiotic therapy should be guided by the most likely infecting organism based upon the clinical circumstances. Prior to the availability of culture results, we favor treatment with a combination of vancomycin and an agent with activity against gram-negative organisms, especially Salmonella and enteric gram-negatives; reasonable choices include ceftriaxone, a fluoroquinolone, and piperacillin-tazobactam.

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Endovascular techniques are emerging as a treatment alternative for infected aneurysm, most commonly for infected aortic aneurysms [117,138-149]. (See 'Role of endovascular techniques' below.) <span>Antibiotic therapy — The initial choice of antibiotic therapy should be guided by the most likely infecting organism based upon the clinical circumstances. Prior to the availability of culture results, we favor treatment with a combination of vancomycin and an agent with activity against gram-negative organisms, especially Salmonella and enteric gram-negatives; reasonable choices include ceftriaxone, a fluoroquinolone, and piperacillin-tazobactam. Antibiotics should be tailored to culture and susceptibility results when they become available. The optimal duration of antibiotic therapy is uncertain and depends on factors, includin

#### Annotation 6229792263436

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite The optimal duration of antibiotic therapy is uncertain and depends on factors, including the immune competence of patient, location of infection, specific bacteria, autogenous versus prosthetic grafts, in situ versus extraanatomic reconstruction, and response to treatment (fever, white count, hemodynamic stability). In general, at least six weeks of parenteral and/or oral antimicrobial therapy is administered for treatment of infected aneurysm. If surgical drainage is performed, this time period commences from the day of surgery.

UpToDate
gatives; reasonable choices include ceftriaxone, a fluoroquinolone, and piperacillin-tazobactam. Antibiotics should be tailored to culture and susceptibility results when they become available. <span>The optimal duration of antibiotic therapy is uncertain and depends on factors, including the immune competence of patient, location of infection, specific bacteria, autogenous versus prosthetic grafts, in situ versus extraanatomic reconstruction, and response to treatment (fever, white count, hemodynamic stability). In general, at least six weeks of parenteral and/or oral antimicrobial therapy is administered for treatment of infected aneurysm. If surgical drainage is performed, this time period commences from the day of surgery. However, there are no data to support a specific duration of antibiotic therapy; in some circumstances, particularly for cases in which autologous vein grafting is used, a shorter durat

#### Annotation 6229794622732

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite However, there are no data to support a specific duration of antibiotic therapy; in some circumstances, particularly for cases in which autologous vein grafting is used, a shorter duration may be sufficient. A longer duration of treatment may be warranted in the setting of antibiotic-resistant organisms, persistently positive cultures, and/or inflammatory markers that are slow to normalize [150]. Suppressive oral antibiotics following completion of intravenous therapy may be warranted for patients reconstructed with prosthetic graft material in situ during active infection [8,151,152].

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weeks of parenteral and/or oral antimicrobial therapy is administered for treatment of infected aneurysm. If surgical drainage is performed, this time period commences from the day of surgery. <span>However, there are no data to support a specific duration of antibiotic therapy; in some circumstances, particularly for cases in which autologous vein grafting is used, a shorter duration may be sufficient. A longer duration of treatment may be warranted in the setting of antibiotic-resistant organisms, persistently positive cultures, and/or inflammatory markers that are slow to normalize [150]. Suppressive oral antibiotics following completion of intravenous therapy may be warranted for patients reconstructed with prosthetic graft material in situ during active infection [8,151,152]. Surgery — Management of infected aneurysms follows the general principles of managing vascular graft infection. The main surgical aim is removal of all necrotic and infected tissue and

#### Annotation 6229797506316

 #Aortite #Maladies-infectieuses-et-tropicales #TopoAortite Surgery — Management of infected aneurysms follows the general principles of managing vascular graft infection. The main surgical aim is removal of all necrotic and infected tissue and management of any ensuing ischemia

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Suppressive oral antibiotics following completion of intravenous therapy may be warranted for patients reconstructed with prosthetic graft material in situ during active infection [8,151,152]. <span>Surgery — Management of infected aneurysms follows the general principles of managing vascular graft infection. The main surgical aim is removal of all necrotic and infected tissue and management of any ensuing ischemia. The decision to pursue vascular reconstruction depends primarily upon the patient's underlying vascular status and the anatomic site of the aneurysm (which determines the likelihood of

#### Flashcard 6231076506892

Question
Which statement is true about the role of vitamin A in the visual cycle?
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Which statement is true about the role of vitamin A in the visual cycle?

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#### Flashcard 6231080439052

Question
2. What is the symptom of vitamin deficiency in a person who refuses to eat yellow and dark green vegetables?
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2. What is the symptom of vitamin deficiency in a person who refuses to eat yellow and dark green vegetables? A A. follicular hyperkeratosis C.pellagra B. osteoporosis D.Wernicke-Korsakoff syndrome

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#### Flashcard 6231081487628

Question
A. follicular hyperkeratosis C.pellagra B. osteoporosis D.Wernicke-Korsakoff syndrome

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2. What is the symptom of vitamin deficiency in a person who refuses to eat yellow and dark green vegetables? A A. follicular hyperkeratosis C.pellagra B. osteoporosis D.Wernicke-Korsakoff syndrome

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#### Flashcard 6231085419788

Question
Define the weighted arithmetic mean.

Formally, the weighted mean of a non-empty finite multiset of data $$\{x_{1},x_{2},\dots ,x_{n}\},$$ with corresponding non-negative weights $${\displaystyle \{w_{1},w_{2},\dots ,w_{n}\}}$$ is

$${\bar {x}}={\frac {\sum \limits _{i=1}^{n}w_{i}x_{i}}{\sum \limits _{i=1}^{n}w_{i}}},$$

which expands to:

$${\bar {x}}={\frac {w_{1}x_{1}+w_{2}x_{2}+\cdots +w_{n}x_{n}}{w_{1}+w_{2}+\cdots +w_{n}}}.$$

Therefore, data elements with a high weight contribute more to the weighted mean than do elements with a low weight. The weights cannot be negative. Some may be zero, but not all of them (since division by zero is not allowed).

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Weighted arithmetic mean - Wikipedia
le {\frac {30}{20+30}}=0.6} Then, apply the weights like this: x ¯ = ( 0.4 × 80 ) + ( 0.6 × 90 ) = 86. {\displaystyle {\bar {x}}=(0.4\times 80)+(0.6\times 90)=86.} Mathematical definition <span>Formally, the weighted mean of a non-empty finite multiset of data { x 1 , x 2 , … , x n } , {\displaystyle \{x_{1},x_{2},\dots ,x_{n}\},} with corresponding non-negative weights { w 1 , w 2 , … , w n } {\displaystyle \{w_{1},w_{2},\dots ,w_{n}\}} is x ¯ = ∑ i = 1 n w i x i ∑ i = 1 n w i , {\displaystyle {\bar {x}}={\frac {\sum \limits _{i=1}^{n}w_{i}x_{i}}{\sum \limits _{i=1}^{n}w_{i}}},} which expands to: x ¯ = w 1 x 1 + w 2 x 2 + ⋯ + w n x n w 1 + w 2 + ⋯ + w n . {\displaystyle {\bar {x}}={\frac {w_{1}x_{1}+w_{2}x_{2}+\cdots +w_{n}x_{n}}{w_{1}+w_{2}+\cdots +w_{n}}}.} Therefore, data elements with a high weight contribute more to the weighted mean than do elements with a low weight. The weights cannot be negative. Some may be zero, but not all of them (since division by zero is not allowed). The formulas are simplified when the weights are normalized such that they sum up to 1 {\displaystyle 1} , i.e.: ∑ i = 1 n w i ′ = 1 {\displaystyle \sum _{i=1}^{n}{w_{i}'}=1} . For such

#### Annotation 6231124741388

 #Hypercalcemie The relationship between these units is defined by the following equations: mmol/L = [mg/dL x 10] ÷ mol wt mEq/L = mmol/L x valence Since the molecular weight of calcium is 40 and the valence is +2, 1 mg/dL is equivalent to 0.25 mmol/L and 0.5 mEq/L. Thus, the normal range of total serum calcium concentration of 8.8 to 10.3 mg/dL is equivalent to 2.2 to 2.6 mmol/L and 4.4 to 5.2 mEq/L

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019. INTRODUCTION — The plasma (or serum) calcium concentration is usually reported in units of mg/dL in the United States, in mmol/L in many other countries, and in mEq/L by some laboratories. <span>The relationship between these units is defined by the following equations: mmol/L = [mg/dL x 10] ÷ mol wt mEq/L = mmol/L x valence Since the molecular weight of calcium is 40 and the valence is +2, 1 mg/dL is equivalent to 0.25 mmol/L and 0.5 mEq/L. Thus, the normal range of total serum calcium concentration of 8.8 to 10.3 mg/dL is equivalent to 2.2 to 2.6 mmol/L and 4.4 to 5.2 mEq/L. DETERMINANTS OF THE SERUM CALCIUM CONCENTRATION — The total serum calcium concentration consists of three fractions [1,2]: ●Approximately 15 percent is bound to multiple organic and in

#### Annotation 6231125789964

 #Hypercalcemie The total serum calcium concentration consists of three fractions [1,2]: ● Approximately 15 percent is bound to multiple organic and inorganic anions such as sulfate, phosphate, lactate, and citrate. ● Approximately 40 percent is bound to proteins, primarily albumin. ● The remaining 45 percent circulates as physiologically active ionized (or free) calcium. The ionized serum calcium concentration is tightly regulated by parathyroid hormone (PTH) and vitamin D, and can be modified by a variety of factors

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Eq/L. Thus, the normal range of total serum calcium concentration of 8.8 to 10.3 mg/dL is equivalent to 2.2 to 2.6 mmol/L and 4.4 to 5.2 mEq/L. DETERMINANTS OF THE SERUM CALCIUM CONCENTRATION — <span>The total serum calcium concentration consists of three fractions [1,2]: ●Approximately 15 percent is bound to multiple organic and inorganic anions such as sulfate, phosphate, lactate, and citrate. ●Approximately 40 percent is bound to proteins, primarily albumin. ●The remaining 45 percent circulates as physiologically active ionized (or free) calcium. The ionized serum calcium concentration is tightly regulated by parathyroid hormone (PTH) and vitamin D, and can be modified by a variety of factors. (See 'Change in ionized fraction but not total calcium' below.) The wide range in the normal total serum calcium concentration is probably due to variations in the serum concentration

#### Annotation 6231126838540

 #Hypercalcemie The wide range in the normal total serum calcium concentration is probably due to variations in the serum concentration of albumin and variations in the state of hydration

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lcium concentration is tightly regulated by parathyroid hormone (PTH) and vitamin D, and can be modified by a variety of factors. (See 'Change in ionized fraction but not total calcium' below.) <span>The wide range in the normal total serum calcium concentration is probably due to variations in the serum concentration of albumin and variations in the state of hydration. Thus, measurement of the total serum calcium concentration alone is frequently misleading, since this parameter can change without affecting the concentration of ionized calcium [3]. I

#### Annotation 6231127887116

 #Hypercalcemie Change in total but not ionized calcium — An abnormal total serum calcium concentration in the presence of a normal ionized calcium concentration can occur in patients with hypoalbuminemia, hyperalbuminemia, and multiple myeloma.

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his parameter can change without affecting the concentration of ionized calcium [3]. In addition, the ionized fraction can change without an alteration in the total serum calcium concentration. <span>Change in total but not ionized calcium — An abnormal total serum calcium concentration in the presence of a normal ionized calcium concentration can occur in patients with hypoalbuminemia, hyperalbuminemia, and multiple myeloma. If the total serum calcium is low but the ionized calcium is normal, it is called pseudohypocalcemia. If the total serum calcium is high in the setting of a normal ionized calcium, it i

#### Annotation 6231128935692

 #Hypercalcemie Hypoalbuminemia — The total serum calcium concentration will change in parallel to the albumin concentration. Thus, hypoalbuminemia due to hepatic or renal disease is associated with hypocalcemia. By comparison, globulins only minimally bind calcium, and changes in the globulin level are usually not associated with dramatic changes in the calcium concentration, with the occasional exception of marked hyperglobulinemia in multiple myeloma

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lcium is low but the ionized calcium is normal, it is called pseudohypocalcemia. If the total serum calcium is high in the setting of a normal ionized calcium, it is called pseudohypercalcemia. <span>Hypoalbuminemia — The total serum calcium concentration will change in parallel to the albumin concentration. Thus, hypoalbuminemia due to hepatic or renal disease is associated with hypocalcemia. By comparison, globulins only minimally bind calcium, and changes in the globulin level are usually not associated with dramatic changes in the calcium concentration, with the occasional exception of marked hyperglobulinemia in multiple myeloma. In the setting of hypoalbuminemia, clinicians have attempted to estimate total serum calcium concentrations using a variety of correction formulas that take into account albumin concen

#### Annotation 6231129984268

 #Hypercalcemie Traditionally, one of the most widely utilized equations to estimate the total calcium concentration in clinical practice assumes the serum calcium to fall by 0.8 mg/dL (0.2 mmol/L) for every 1.0 g/dL (10 g/L) fall in the serum albumin concentration

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In the setting of hypoalbuminemia, clinicians have attempted to estimate total serum calcium concentrations using a variety of correction formulas that take into account albumin concentrations. <span>Traditionally, one of the most widely utilized equations to estimate the total calcium concentration in clinical practice assumes the serum calcium to fall by 0.8 mg/dL (0.2 mmol/L) for every 1.0 g/dL (10 g/L) fall in the serum albumin concentration. Thus, in this calculation, the measured serum calcium concentration would be corrected for the presence of hypoalbuminemia using the following equation: Corrected [Ca] = Measured total

#### Annotation 6231131032844

 #Hypercalcemie Despite widespread use of this formula in clinical practice over the last several decades, more contemporary studies suggest the accuracy of this estimate is quite poor in a variety of populations, including patients hospitalized with critical illness and patients with advanced-stage chronic kidney disease (CKD) [4-10]. The poor performance of calcium-correction formulas in patients with critical illness and CKD may be partially explained by the presence of metabolic acidosis, which can lead to an underestimate of the ionized calcium

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ng the following equation: Corrected [Ca] = Measured total [Ca] + (0.8 x (4.0 - [alb])) where the serum calcium and albumin concentrations are measured in units of mg/dL and g/dL, respectively. <span>Despite widespread use of this formula in clinical practice over the last several decades, more contemporary studies suggest the accuracy of this estimate is quite poor in a variety of populations, including patients hospitalized with critical illness and patients with advanced-stage chronic kidney disease (CKD) [4-10]. The poor performance of calcium-correction formulas in patients with critical illness and CKD may be partially explained by the presence of metabolic acidosis, which can lead to an underestimate of the ionized calcium (see 'Acid-base disorders' below). Based upon these studies highlighting the potential inaccuracies of calcium-correction formulas, measurement of ionized calcium remains the gold stand

#### Annotation 6231132081420

 #Hypercalcemie Hyperalbuminemia — An elevation in serum albumin, leading to a rise in serum calcium, can be induced by extracellular volume depletion or by fluid movement out of the vascular space due, for example, to a tight tourniquet [11]. Hyperalbuminemia has also been reported in athletes who consume very high-protein diets (more than 2 g of protein per kg of body weight per day)

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below). Based upon these studies highlighting the potential inaccuracies of calcium-correction formulas, measurement of ionized calcium remains the gold standard for evaluating calcium status. <span>Hyperalbuminemia — An elevation in serum albumin, leading to a rise in serum calcium, can be induced by extracellular volume depletion or by fluid movement out of the vascular space due, for example, to a tight tourniquet [11]. Hyperalbuminemia has also been reported in athletes who consume very high-protein diets (more than 2 g of protein per kg of body weight per day) [12]. Multiple myeloma — Myeloma can induce pseudohypercalcemia by a mechanism other than hyperalbuminemia. Rarely, a monoclonal myeloma protein binds calcium with high affinity, potent

#### Annotation 6231133129996

 #Hypercalcemie Multiple myeloma — Myeloma can induce pseudohypercalcemia by a mechanism other than hyperalbuminemia. Rarely, a monoclonal myeloma protein binds calcium with high affinity, potentially leading to a marked elevation in the total serum calcium concentration [13-15]. Since multiple myeloma is commonly associated with true hypercalcemia related to osteolytic lesions, measurement of the ionized calcium can help to differentiate these entities. Likewise, the absence of hypercalcemic symptoms is often a major clue suggesting that the ionized fraction is normal in pseudohypercalcemia and that therapy aimed at correcting the hypercalcemia is not indicated.

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, for example, to a tight tourniquet [11]. Hyperalbuminemia has also been reported in athletes who consume very high-protein diets (more than 2 g of protein per kg of body weight per day) [12]. <span>Multiple myeloma — Myeloma can induce pseudohypercalcemia by a mechanism other than hyperalbuminemia. Rarely, a monoclonal myeloma protein binds calcium with high affinity, potentially leading to a marked elevation in the total serum calcium concentration [13-15]. Since multiple myeloma is commonly associated with true hypercalcemia related to osteolytic lesions, measurement of the ionized calcium can help to differentiate these entities. Likewise, the absence of hypercalcemic symptoms is often a major clue suggesting that the ionized fraction is normal in pseudohypercalcemia and that therapy aimed at correcting the hypercalcemia is not indicated. The hyperproteinemia in myeloma can also cause a spurious elevation in the serum phosphate concentration [16]. The mechanism involves interference with the molybdate assay commonly used

#### Annotation 6231134178572

 #Hypercalcemie The hyperproteinemia in myeloma can also cause a spurious elevation in the serum phosphate concentration [16]. The mechanism involves interference with the molybdate assay commonly used to measure the serum phosphate concentration

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ce of hypercalcemic symptoms is often a major clue suggesting that the ionized fraction is normal in pseudohypercalcemia and that therapy aimed at correcting the hypercalcemia is not indicated. <span>The hyperproteinemia in myeloma can also cause a spurious elevation in the serum phosphate concentration [16]. The mechanism involves interference with the molybdate assay commonly used to measure the serum phosphate concentration. Change in ionized fraction but not total calcium — Physiologically important changes in the ionized calcium concentration may occur without an alteration in the total serum calcium con

#### Annotation 6231135227148

 #Hypercalcemie Acid-base disorders can lead to changes in the ionized calcium concentration. An elevation in extracellular pH (alkalemia) increases the binding of calcium to albumin, thereby lowering the serum ionized calcium concentration [17]. The fall in ionized calcium with acute respiratory alkalosis is approximately 0.16 mg/dL (0.04 mmol/L or 0.08 mEq/L) for each 0.1 unit increase in pH [17]. Thus, acute respiratory alkalosis, as in the hyperventilation syndrome, can induce symptoms of hypocalcemia, including cramps, paresthesias, tetany, and seizures, although the alkalosis is likely to be of primary importance.

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on but not total calcium — Physiologically important changes in the ionized calcium concentration may occur without an alteration in the total serum calcium concentration. Acid-base disorders — <span>Acid-base disorders can lead to changes in the ionized calcium concentration. An elevation in extracellular pH (alkalemia) increases the binding of calcium to albumin, thereby lowering the serum ionized calcium concentration [17]. The fall in ionized calcium with acute respiratory alkalosis is approximately 0.16 mg/dL (0.04 mmol/L or 0.08 mEq/L) for each 0.1 unit increase in pH [17]. Thus, acute respiratory alkalosis, as in the hyperventilation syndrome, can induce symptoms of hypocalcemia, including cramps, paresthesias, tetany, and seizures, although the alkalosis is likely to be of primary importance. The same relationship is true in vitro when the pH is changed in specimens of whole blood or serum [18]. There is also a significant fall in the ionized calcium concentration in chronic

#### Annotation 6231136275724

 #Hypercalcemie The binding of calcium to albumin that is induced by an elevation in extracellular pH may be important in patients with severe CKD who often have both hypocalcemia and metabolic acidosis, which will tend to raise the ionized calcium concentration. Treatment of the metabolic acidosis with bicarbonate therapy or dialysis can lower the ionized calcium concentration [20,21], which may exacerbate preexisting hypocalcemia and precipitate symptoms such as tetany [21]

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calcium underestimated the diagnosis of hypercalcemia in incident kidney transplant recipients [5]. This was explained primarily by the high prevalence of metabolic acidosis in these patients. <span>The binding of calcium to albumin that is induced by an elevation in extracellular pH may be important in patients with severe CKD who often have both hypocalcemia and metabolic acidosis, which will tend to raise the ionized calcium concentration. Treatment of the metabolic acidosis with bicarbonate therapy or dialysis can lower the ionized calcium concentration [20,21], which may exacerbate preexisting hypocalcemia and precipitate symptoms such as tetany [21]. Parathyroid hormone — PTH may decrease the binding of calcium to albumin and therefore increase ionized calcium at the expense of the protein-bound fraction, resulting in an increased

#### Annotation 6231137324300

 #Hypercalcemie Hyperphosphatemia — Acute hyperphosphatemia (as with phosphate release from cells due to a marked increase in cell breakdown) can reduce the ionized serum calcium concentration by binding to circulating calcium. The total serum calcium concentration will also fall in a short period of time as the calcium-phosphate precipitates and is deposited in soft tissues.

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ct of PTH on protein binding of calcium does not have diagnostic implications. (See "Primary hyperparathyroidism: Diagnosis, differential diagnosis, and evaluation", section on 'Introduction'.) <span>Hyperphosphatemia — Acute hyperphosphatemia (as with phosphate release from cells due to a marked increase in cell breakdown) can reduce the ionized serum calcium concentration by binding to circulating calcium. The total serum calcium concentration will also fall in a short period of time as the calcium-phosphate precipitates and is deposited in soft tissues. (See "Etiology of hypocalcemia in adults".) SUMMARY ●The total serum calcium concentration consists of three fractions (see 'Determinants of the serum calcium concentration' above): •15

#### Annotation 6231145450764

 #idris2 In conventional programming languages, there is a clear distinction between types and values. For example, in Haskell, the following are types, representing integers, characters, lists of characters, and lists of any value respectively:

Introduction — Idris2 0.0 documentation
ign Function Interface Theorem Proving Frequently Asked Questions Implementation Notes Idris2 Reference Guide Idris2 Docs » A Crash Course in Idris 2 » Introduction Edit on GitHub Introduction¶ <span>In conventional programming languages, there is a clear distinction between types and values. For example, in Haskell, the following are types, representing integers, characters, lists of characters, and lists of any value respectively: Int, Char, [Char], [a] Correspondingly, the following values are examples of inhabitants of those types: 42, ’a’, "Hello world!", [2,3,4,5,6] In a language with dependent types, however

#### Annotation 6231150431500

 #idris The documentation for Idris 2 has been published under the Creative Commons CC0 License. As such to the extent possible under law, The Idris Community has waived all copyright and related or neighboring rights to Documentation for Idris.