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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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An aortic aneurysm can occur as a result of trauma, infection, or, most commonly, from an intrinsic abnormality in the elastin and collagen components of the aortic wall. While definite genetic abnormalities were identified in true genetic syndromes (Marfan, Elher-Danlos and others) associated with aortic aneurysms, both thoracic and abdominal aortic aneurysms demonstrate a strong genetic component in their aetiology.
The risk of aneurysm enlargement may be diminished with attention to the patient's blood pressure, smoking and cholesterol levels. There have been proposals to introduce ultrasound scans as a screening tool for those most at risk: men over the age of 65. The tetracycline antibiotic doxycycline is currently being investigated for use as a potential drug in the prevention of aortic aneurysm due to its metalloproteinase inhibitor and collagen stabilizing properties. In contrast, fluoroquinolones antibiotics are being investigated as a potential contributor to aortic aneurysms, given their tendency to break down collagen fibrils.
Anacetrapib is a cholesteryl ester transfer protein inhibitor that raises high-density lipoprotein (HDL) cholesterol and reduces low-density lipoprotein (LDL) cholesterol.
Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin
Elevating the amount of HDL cholesterol in the abdominal area of the aortic artery in mice both reduced the size of aneurysms that had already grown and prevented abdominal aortic aneurysms from forming at all. In short, raising HDL cholesterol is beneficial because it induces programmed cell death. The walls of a failing aorta are replaced and strengthened. New lesions should not form at all when using this drug.
The occurrence of AAA varies by ethnicity. In the United Kingdom the rate of AAA in Caucasian men older than 65 years is about 4.7%, while in Asian men it is 0.45%. It is also less common in individuals of African, and Hispanic heritage. They occur four times more often in men than women.
There are at least 13,000 deaths yearly in the U.S. secondary to AAA rupture. The peak number of new cases per year among males is around 70 years of age, the percentage of males affected over 60 years is 2–6%. The frequency is much higher in smokers than in non-smokers (8:1), and the risk decreases slowly after smoking cessation. In the U.S., the incidence of AAA is 2–4% in the adult population.
Rupture of the AAA occurs in 1–3% of men aged 65 or more, the mortality is 70–95%.
Although the exact cause is unknown, some risk factors associated with individuals with IAA are:
Tobacco Use: Cigarette smoking and other forms of tobacco use appear to increase your risk of aortic aneurysms. In addition to the damaging effects that smoking causes directly to the arteries, smoking contributes to the buildup of fatty plaques in your arteries (atherosclerosis) and high blood pressure. Smoking can also cause your aneurysm to grow faster by further damaging your aorta.
Hardening of the arteries (atherosclerosis). Atherosclerosis occurs when fat and other substances build up on the lining of a blood vessel, increasing your risk of an aneurysm.
Infection in the aorta (vasculitis). In rare cases, abdominal aortic aneurysm may be caused by an infection or inflammation that weakens a section of the aortic wall.
Conservative management is indicated in people where repair carries a high risk of mortality and in patients where repair is unlikely to improve life expectancy. The mainstay of the conservative treatment is smoking cessation.
Surveillance is indicated in small asymptomatic aneurysms (less than 5.5 cm) where the risk of repair exceeds the risk of rupture. As an AAA grows in diameter, the risk of rupture increases. Surveillance until an aneurysm has reached a diameter of 5.5 cm has not been shown to have a higher risk as compared to early intervention.
Inflammatory aortic aneurysm (IAA), also known as Inflammatory abdominal aortic aneurysm (IAAA), is a type of abdominal aortic aneurysm (AAA) where the walls of the aneurysm become thick and inflamed. Similar to AAA, IAA occurs in the abdominal region. IAA is closely associated and believed to be a response to and extensive peri-anuerysmal fibrosis, which is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process IAA accounts for 5-10% of aortic aneurysms. IAA is occurs mainly in a population that is on average younger by 10 years than most AAA patients. Some common symptoms of IAA may include back pain, abdominal tenderness, fevers, weight loss or elevated Erythrocyte sedimentation rate (ESR) levels. Corticosteroids and other immunosuppressive drugs have been found to decrease symptoms and the degree of peri-aortic inflammation and fibrosis
Triple-A syndrome is associated with mutations in the "AAAS" gene, which encodes a protein known as ALADIN (ALacrima Achalasia aDrenal Insufficiency Neurologic disorder). In 2000, Huebner "et al." mapped the syndrome to a 6 cM interval on human chromosome 12q13 near the type II keratin gene cluster. Since inheritance and gene for the association is known, early diagnosis can allow genetic counseling.
Triple-A syndrome or AAA syndrome, also known as achalasia-addisonianism-alacrima syndrome or Allgrove syndrome, is a rare autosomal recessive congenital disorder. In most cases, there is no family history of it. The syndrome was first identified by Jeremy Allgrove and colleagues in 1978. The syndrome involves achalasia, addisonianism (adrenal insufficiency of primary type), and alacrima (insufficiency of tears). Alacrima is usually the earliest manifestation. It is a progressive disorder that can take years to develop the full blown clinical picture.
The first case of eosinophilia–myalgia syndrome was reported to the Centers for Disease Control and Prevention (CDC) in November 1989, although some cases had occurred as early as 2–3 years before this. In total, more than 1,500 cases of EMS were reported to the CDC, as well as at least 37 EMS-associated deaths. After preliminary investigation revealed that the outbreak was linked to intake of tryptophan, the U.S. Food and Drug Administration (FDA) recalled tryptophan supplements in 1989 and banned most public sales in 1990, with other countries following suit.
There is some evidence that children with AS may see a lessening of symptoms; up to 20% of children may no longer meet the diagnostic criteria as adults, although social and communication difficulties may persist. As of 2006, no studies addressing the long-term outcome of individuals with Asperger syndrome are available and there are no systematic long-term follow-up studies of children with AS. Individuals with AS appear to have normal life expectancy, but have an increased prevalence of comorbid psychiatric conditions, such as major depressive disorder and anxiety disorder that may significantly affect prognosis. Although social impairment may be lifelong, the outcome is generally more positive than with individuals with lower functioning autism spectrum disorders; for example, ASD symptoms are more likely to diminish with time in children with AS or HFA. Most students with AS/HFA have average mathematical ability and test slightly worse in mathematics than in general intelligence, but some are gifted in mathematics. AS has potentially been linked to some accomplishments, such as Vernon L. Smith winning the Nobel Memorial Prize in Economic Sciences; however, Smith is self-diagnosed.
Although many attend regular education classes, some children with AS may utilize special education services because of their social and behavioral difficulties. Adolescents with AS may exhibit ongoing difficulty with self care or organization, and disturbances in social and romantic relationships. Despite high cognitive potential, most young adults with AS remain at home, yet some do marry and work independently. The "different-ness" adolescents experience can be traumatic. Anxiety may stem from preoccupation over possible violations of routines and rituals, from being placed in a situation without a clear schedule or expectations, or from concern with failing in social encounters; the resulting stress may manifest as inattention, withdrawal, reliance on obsessions, hyperactivity, or aggressive or oppositional behavior. Depression is often the result of chronic frustration from repeated failure to engage others socially, and mood disorders requiring treatment may develop. Clinical experience suggests the rate of suicide may be higher among those with AS, but this has not been confirmed by systematic empirical studies.
Education of families is critical in developing strategies for understanding strengths and weaknesses; helping the family to cope improves outcomes in children. Prognosis may be improved by diagnosis at a younger age that allows for early interventions, while interventions in adulthood are valuable but less beneficial. There are legal implications for individuals with AS as they run the risk of exploitation by others and may be unable to comprehend the societal implications of their actions.
Although HSP is a progressive condition, the prognosis for individuals with HSP varies greatly. It primarily affects the legs although there can be some upperbody involvement in some individuals. Some cases are seriously disabling while others are less disabling and are compatible with a productive and full life. The majority of individuals with HSP have a normal life expectancy.
Eosinophilia–myalgia syndrome (EMS) is an incurable and sometimes fatal flu-like neurological condition linked to the ingestion of the dietary supplement L-tryptophan. The risk of developing EMS increases with larger doses of tryptophan and increasing age. Some research suggests that certain genetic polymorphisms may be related to the development of EMS. The presence of eosinophilia is a core feature of EMS, along with unusually severe myalgia (muscle pain).
HSP is a group of genetic disorders. It follows general inheritance rules and can be inherited in an autosomal dominant, autosomal recessive or X-linked recessive manner. The mode of inheritance involved has a direct impact on the chances of inheriting the disorder. Over 70 genotypes had been described, and over 50 genetic loci have been linked to this condition. Ten genes have been identified with autosomal dominant inheritance. One of these SPG4 accounts for ~50% of all genetically solved cases cases, or approximately 25% of all HSP cases. Twelve genes are known to be inherited in an autosomal recessive fashion. Collectively this latter group account for ~1/3 cases.
Most altered genes have known function, but for some the function haven’t been identified yet. All of them are listed in the gene list below, including their mode of inheritance. Some examples are spastin (SPG4) and paraplegin (SPG7) are both AAA ATPases.
Frequency estimates vary enormously. In 2015 it was estimated that 37.2 million people globally are affected. A 2003 review of epidemiological studies of children found autism rates ranging from 0.03 to 4.84 per 1,000, with the ratio of autism to Asperger syndrome ranging from 1.5:1 to 16:1; combining the geometric mean ratio of 5:1 with a conservative prevalence estimate for autism of 1.3 per 1,000 suggests indirectly that the prevalence of AS might be around 0.26 per 1,000. Part of the variance in estimates arises from differences in diagnostic criteria. For example, a relatively small 2007 study of 5,484 eight-year-old children in Finland found 2.9 children per 1,000 met the ICD-10 criteria for an AS diagnosis, 2.7 per 1,000 for Gillberg and Gillberg criteria, 2.5 for DSM-IV, 1.6 for Szatmari "et al.", and 4.3 per 1,000 for the union of the four criteria. Boys seem to be more likely to have AS than girls; estimates of the sex ratio range from 1.6:1 to 4:1, using the Gillberg and Gillberg criteria. Females with autism spectrum disorders may be underdiagnosed.
Anxiety disorder and major depressive disorder are the most common conditions seen at the same time; comorbidity of these in persons with AS is estimated at 65%. Reports have associated AS with medical conditions such as aminoaciduria and ligamentous laxity, but these have been case reports or small studies and no factors have been associated with AS across studies. One study of males with AS found an increased rate of epilepsy and a high rate (51%) of nonverbal learning disorder. AS is associated with tics, Tourette syndrome, and bipolar disorder, and the repetitive behaviors of AS have many similarities with the symptoms of obsessive–compulsive disorder and obsessive–compulsive personality disorder. However many of these studies are based on clinical samples or lack standardized measures; nonetheless, comorbid conditions are relatively common.