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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)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Historically, medical practitioners expected a person to present with three findings. This classic triad is 1: haematuria, which is when there is blood present in the urine, 2: flank pain, which is pain on the side of the body between the hip and ribs, and 3: an abdominal mass, similar to bloating but larger. It is now known that this classic triad of symptoms only occurs in 10–15% of cases, and is usually indicative that the renal cell carcinoma (RCC) is in an advanced stage. Today, RCC is often asymptomatic (meaning few to no symptoms) and is generally detected incidentally when a person is being examined for other ailments.
Other signs and symptom may include haematuria; loin pain; abdominal mass; malaise, which is a general feeling of unwellness; weight loss and/or loss of appetite; anaemia resulting from depression of erythropoietin; erythrocytosis (increased production of red blood cells) due to increased erythropoietin secretion; varicocele, which is seen in males as an enlargement of the pampiniform plexus of veins draining the testis (more often the left testis) hypertension (high blood pressure) resulting from secretion of renin by the tumour; hypercalcemia, which is elevation of calcium levels in the blood; sleep disturbance or night sweats; recurrent fevers; and chronic fatigue.
Renal cell carcinoma (RCC) is not a single entity, but rather a collection of different types of tumours, each derived from the various parts of the nephron (epithelium or renal tubules) and possessing distinct genetic characteristics, histological features, and, to some extent, clinical phenotypes.
Array-based karyotyping can be used to identify characteristic chromosomal aberrations in renal tumors with challenging morphology. Array-based karyotyping performs well on paraffin embedded tumours and is amenable to routine clinical use. See also Virtual Karyotype for CLIA certified laboratories offering array-based karyotyping of solid tumours.
The 2004 World Health Organization (WHO) classification of genitourinary tumours recognizes over 40 subtypes of renal neoplasms. Since the publication of the latest iteration of the WHO classification in 2004, several novel renal tumour subtypes have been described:
- Clear cell papillary renal cell carcinoma and Clear cell renal cell carcinoma with smooth muscle stroma
- Mucinous tubular and spindle cell carcinoma (MTSCC)
- Multilocular cystic clear cell renal cell carcinoma
- Tubulocystic renal cell carcinoma
- Thyroid-like follicular renal cell carcinoma
- Acquired cystic kidney disease-associated renal cell carcinoma
- Renal cell carcinoma with t(6;11) translocation (TFEB)
- Hybrid oncocytoma/chromophobe renal cell carcinoma
- Hereditary leiomyomatosis and renal cell carcinoma(HLRCC)
Since pancreatic cancer usually does not cause recognizable symptoms in its early stages, the disease is typically not diagnosed until it has spread beyond the pancreas itself. This is one of the main reasons for the generally poor survival rates. Exceptions to this are the functioning PanNETs, where over-production of various active hormones can give rise to symptoms (which depend on the type of hormone).
Bearing in mind that the disease is rarely diagnosed before the age of 40, common symptoms of pancreatic adenocarcinoma occurring before diagnosis include:
- Pain in the upper abdomen or back, often spreading from around the stomach to the back. The location of the pain can indicate the part of the pancreas where a tumor is located. The pain may be worse at night and may increase over time to become severe and unremitting. It may be slightly relieved by bending forward. In the UK, about half of new cases of pancreatic cancer are diagnosed following a visit to a hospital emergency department for pain or jaundice. In up to two-thirds of people abdominal pain is the main symptom, for 46% of the total accompanied by jaundice, with 13% having jaundice without pain.
- Jaundice, a yellow tint to the whites of the eyes or skin, with or without pain, and possibly in combination with darkened urine. This results when a cancer in the head of the pancreas obstructs the common bile duct as it runs through the pancreas.
- Unexplained weight loss, either from loss of appetite, or loss of exocrine function resulting in poor digestion.
- The tumor may compress neighboring organs, disrupting digestive processes and making it difficult for the stomach to empty, which may cause nausea and a feeling of fullness. The undigested fat leads to foul-smelling, fatty feces that are difficult to flush away. Constipation is common.
- At least 50% of people with pancreatic adenocarcinoma have diabetes at the time of diagnosis. While long-standing diabetes is a known risk factor for pancreatic cancer (see Risk factors), the cancer can itself cause diabetes, in which case recent onset of diabetes could be considered an early sign of the disease. People over 50 who develop diabetes have eight times the usual risk of developing pancreatic adenocarcinoma within three years, after which the relative risk declines.
Other common manifestations of the disease include: weakness and tiring easily; dry mouth; sleep problems; and a palpable abdominal mass."
Up to 10% of invasive cancers are related to radiation exposure, including both ionizing radiation and non-ionizing radiation. Additionally, the vast majority of non-invasive cancers are non-melanoma skin cancers caused by non-ionizing ultraviolet radiation. Ultraviolet's position on the electromagnetic spectrum is on the boundary between ionizing and non-ionizing radiation. Non-ionizing radio frequency radiation from mobile phones, electric power transmission, and other similar sources have been described as a possible carcinogen by the World Health Organization's International Agency for Research on Cancer, but the link remains unproven.
Exposure to ionizing radiation is known to increase the future incidence of cancer, particularly leukemia. The mechanism by which this occurs is well understood, but quantitative models predicting the level of risk remain controversial. The most widely accepted model posits that the incidence of cancers due to ionizing radiation increases linearly with effective radiation dose at a rate of 5.5% per sievert. If the linear model is correct, then natural background radiation is the most hazardous source of radiation to general public health, followed by medical imaging as a close second.
Various degrees of intensity and locations of epilepsy are associated with malformations of cortical development. Researchers suggest that approximately 40% of children diagnosed with drug-resistant epilepsy have some degree of cortical malformation.
Lissencephaly (to which pachygyria is most closely linked) is associated with severe mental retardation, epilepsy, and motor disability. Two characteristics of lissencephaly include its absence of convolutions (agyria) and decreased presence of convolutions (pachygyria). The types of seizures associated with lissencephaly include:
- persisting spasms
- focal seizures
- tonic seizures
- atypical seizures
- atonic seizures
Other possible symptoms of lissencephaly include telecanthus, estropia, hypertelorism, varying levels of mental retardation, cerebellar hypoplasia, corpus callosum aplasia, and decreased muscle tone and tendon reflexes. Over 90% of children affected with lissencephaly have seizures.
Patients with subcortical band heterotopia (another disorder associated with pachygyria) typically have milder symptoms and their cognitive function is closely linked to the thickness of the subcortical band and the degree of pachygyria present.
According to the prevalent model, any radiation exposure can increase the risk of cancer. Typical contributors to such risk include natural background radiation, medical procedures, occupational exposures, nuclear accidents, and many others. Some major contributors are discussed below.
The prognosis for children with NMDs varies depending on the specific disorder and the degree of brain abnormality and subsequent neurological signs and symptoms.
Symptoms vary according to the abnormality, but often feature poor muscle tone and motor function, seizures, developmental delays, mental retardation, failure to grow and thrive, difficulties with feeding, swelling in the extremities, and a smaller than normal head. Most infants with an NMD appear normal, but some disorders have characteristic facial or skull features that can be recognized by a neurologist.
Microcephalic osteodysplastic primordial dwarfism (MOPD) type II is an autosomal multisystem disorder including severe pre- and post-natal growth retardation, microcephaly with Seckel syndrome-like facial appearance, and distinctive skeletal alterations. Usually those affected have mild to moderate mental retardation. This female child is the first born of nonconsanguineous parents at 35 weeks gestation through a cesarean section due to intrauterine growth retardation. She had a retarded psychomotor development and was repeatedly hospitalized during her first six months of life due to recurring respiratory infections. Her electroencephalography, auditory brainstem response evaluation, and chromosomal analysis were relatively normal. A brain MRI revealed thickened cerebral cortices with few and large gyri prominently in the frontal and posterior temporal regions, incomplete development of the Sylvian fissures, and dilatation of the posterior horns of the lateral ventricles (colpocephaly). Usually only mild brain malformations are associated with MOPD type II. The imaging findings of this child’s brain most likely represent diffuse pachygyria, a mild form of lissencephaly. This child’s neurodevelopmental findings were mild when compared to previous reports of a well-defined chromosome 17-linked and X-linked lissencephaly in a bedridden patient with severe developmental delays.
The condition is usually seen in athletic individuals typically between 10–14 years of age. Following a strain or partial rupture of patellar ligament the patient develops a traction ‘tendinitis’ characterized by pain and point tenderness at the inferior (lower) pole of the patella associated with focal swelling.
Children with cerebral palsy are particularly prone to SLJ 4.
Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. The body produces insulin when glucose starts to be released into the bloodstream from the digestion of carbohydrates in the diet. Normally this insulin response triggers glucose being taken into body cells, to be used for energy, and inhibits the body from using fat for energy. The concentration of glucose in the blood decreases as a result, staying within the normal range even when a large amount of carbohydrates is consumed. When the body produces insulin under conditions of insulin resistance, the cells are resistant to the insulin and are unable to use it as effectively, leading to high blood sugar. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level. This often remains undetected and can contribute to the development of type 2 diabetes or latent autoimmune diabetes of adults. Although this type of chronic insulin resistance is harmful, during acute illness it is actually a well-evolved protective mechanism. Recent investigations have revealed that insulin resistance helps to conserve the brain's glucose supply by preventing muscles from taking up excessive glucose. In theory, insulin resistance should even be strengthened under harsh metabolic conditions such as pregnancy, during which the expanding fetal brain demands more glucose.
People who develop type 2 diabetes usually pass through earlier stages of insulin resistance and prediabetes, although those often go undiagnosed. Insulin resistance is a syndrome (a set of signs and symptoms) resulting from reduced insulin activity; it is also part of a larger constellation of symptoms called the metabolic syndrome.
Insulin resistance may also develop in patients who have recently experienced abdominal or bariatric procedures. This acute form of insulin resistance that may result post-operatively tends to increase over the short term, with sensitivity to insulin typically returning to patients after about five days.
Approximately 33% of people with influenza are asymptomatic.
Symptoms of influenza can start quite suddenly one to two days after infection. Usually the first symptoms are chills or a chilly sensation, but fever is also common early in the infection, with body temperatures ranging from 38 to 39 °C (approximately 100 to 103 °F). Many people are so ill that they are confined to bed for several days, with aches and pains throughout their bodies, which are worse in their backs and legs. Symptoms of influenza may include:
- Fever and extreme coldness (chills shivering, shaking (rigor))
- Cough
- Nasal congestion
- Vomiting
- Runny nose
- Sneezing
- Body aches, especially joints and throat
- Fatigue
- Headache
- Irritated, watering eyes
- Reddened eyes, skin (especially face), mouth, throat and nose
- Petechial rash
- In children, gastrointestinal symptoms such as diarrhea and abdominal pain, (may be severe in children with influenza B)
It can be difficult to distinguish between the common cold and influenza in the early stages of these infections. Influenza is a mixture of symptoms of common cold and pneumonia, body ache, headache, and fatigue. Diarrhea is not normally a symptom of influenza in adults, although it has been seen in some human cases of the H5N1 "bird flu" and can be a symptom in children. The symptoms most reliably seen in influenza are shown in the adjacent table.
Since antiviral drugs are effective in treating influenza if given early (see treatment section, below), it can be important to identify cases early. Of the symptoms listed above, the combinations of fever with cough, sore throat and/or nasal congestion can improve diagnostic accuracy. Two decision analysis studies suggest that "during local outbreaks" of influenza, the prevalence will be over 70%, and thus patients with any of these combinations of symptoms may be treated with neuraminidase inhibitors without testing. Even in the absence of a local outbreak, treatment may be justified in the elderly during the influenza season as long as the prevalence is over 15%.
The available laboratory tests for influenza continue to improve. The United States Centers for Disease Control and Prevention (CDC) maintains an up-to-date summary of available laboratory tests. According to the CDC, rapid diagnostic tests have a sensitivity of 50–75% and specificity of 90–95% when compared with viral culture. These tests may be especially useful during the influenza season (prevalence=25%) but in the absence of a local outbreak, or peri-influenza season (prevalence=10%).
Occasionally, influenza can cause severe illness including primary viral pneumonia or secondary bacterial pneumonia. The obvious symptom is trouble breathing. In addition, if a child (or presumably an adult) seems to be getting better and then relapses with a high fever, that is a danger sign since this relapse can be bacterial pneumonia.
The dry scaling appearance is most noticeable during the winter as a result of dry air inside people's homes. During the summer, tanning of the surrounding normal skin makes the pale patches of pityriasis alba more prominent.
Individual lesions develop through 3 stages and sometimes are itchy:
1. Raised and red – although the redness is often mild and not noticed by parents
2. Raised and pale
3. Smooth flat pale patches
Lesions are round or oval raised or flat, of 0.5–2 cm in size although may be larger if they occur on the body (up to 4 cm), and usually number from 4 or 5 to over 20. The patches are dry with very fine scales. They most commonly occur on the face (cheeks), but in 20% appear also on the upper arms, neck, or shoulders.
The diagnostic differential should consider tinea and vitiligo amongst other causative factors.
These depend on poorly understood variations in individual biology and consequently may not be found with all people diagnosed with insulin resistance.
- Increased hunger
- Lethargy (tiredness)
- Brain fogginess and inability to focus
- High blood sugar
- Weight gain, fat storage, difficulty losing weight – for most people, excess weight is from high subcutaneous fat storage; the fat in IR is generally stored in and around abdominal organs in both males and females; it is currently suspected that hormones produced in that fat are a precipitating cause of insulin resistance
- Increased blood cholesterol levels
- Increased blood pressure; many people with hypertension are either diabetic or pre-diabetic and have elevated insulin levels due to insulin resistance; one of insulin's effects is to control arterial wall tension throughout the body
An increase in the number of white blood cells in circulation is called leukocytosis. This increase is most commonly caused by inflammation. There are four major causes: increase of production in bone marrow, increased release from storage in bone marrow, decreased attachment to veins and arteries, decreased uptake by tissues. Leukocytosis may affect one or more cell lines and can be neutrophilic, eosinophilic, basophilic, monocytosis, or lymphocytosis.
A range of disorders can cause decreases in white blood cells. This type of white blood cell decreased is usually the neutrophil. In this case the decrease may be called neutropenia or granulocytopenia. Less commonly, a decrease in lymphocytes (called lymphocytopenia or lymphopenia) may be seen.
Sinding-Larsen and Johansson syndrome, named after Swedish surgeon Sven Christian Johansson (1880-1959), and Christian Magnus Falsen Sinding-Larsen (1866-1930), a Norwegian physician, is an analogous condition to Osgood–Schlatter disease involving the patellar tendon and the lower margin of the patella bone, instead of the upper margin of the tibia, as is the case in Osgood-Schlatter. This variant was discovered in 1908, during a winter indoor Olympic qualifier event in Scandinavia. Sever's disease is a similar condition affecting the heel.
This condition called Sinding-Larsen and Johansson syndrome was described independently by Sinding-Larsen in 1921 and Johansson in 1922.
A wide range of symptoms can indicate if a person has polymyalgia rheumatica. The classic symptoms include:
- Pain and stiffness (moderate to severe) in the neck, shoulders, upper arms, thighs, and hips, which inhibits activity, especially in the morning/after sleeping. Pain can also occur in the groin area and in the buttocks. The pain can be limited to one of these areas as well. It is a disease of the "girdles" meaning shoulder girdle or pelvic girdle.
- Fatigue and lack of appetite (possibly leading to weight loss) are also indicative of polymyalgia rheumatica.
- Anemia
- An overall feeling of illness or flu-like symptoms.
- Low-grade (mild) fever or abnormal temperature is sometimes present.
- In most people, it is characterized by constant fatigue, weakness and sometimes exhaustion.
About 15% of people who are diagnosed with polymyalgia rheumatica also have temporal arteritis, and about 50% of people with temporal arteritis have polymyalgia rheumatica. Some symptoms of temporal arteritis include headaches, scalp tenderness, jaw or facial soreness, distorted vision, or aching in the limbs caused by decreased blood flow, and fatigue.
Influenza, commonly known as "the flu", is an infectious disease caused by an influenza virus. Symptoms can be mild to severe. The most common symptoms include: a high fever, runny nose, sore throat, muscle pains, headache, coughing, and feeling tired. These symptoms typically begin two days after exposure to the virus and most last less than a week. The cough, however, may last for more than two weeks. In children, there may be nausea and vomiting, but these are not common in adults. Nausea and vomiting occur more commonly in the unrelated infection gastroenteritis, which is sometimes inaccurately referred to as "stomach flu" or "24-hour flu". Complications of influenza may include viral pneumonia, secondary bacterial pneumonia, sinus infections, and worsening of previous health problems such as asthma or heart failure.
Three types of influenza viruses affect people, called Type A, Type B, and Type C. Usually, the virus is spread through the air from coughs or sneezes. This is believed to occur mostly over relatively short distances. It can also be spread by touching surfaces contaminated by the virus and then touching the mouth or eyes. A person may be infectious to others both before and during the time they are showing symptoms. The infection may be confirmed by testing the throat, sputum, or nose for the virus. A number of rapid tests are available; however, people may still have the infection if the results are negative. A type of polymerase chain reaction that detects the virus's RNA is more accurate.
Frequent hand washing reduces the risk of viral spread. Wearing a surgical mask is also useful. Yearly vaccinations against influenza are recommended by the World Health Organization for those at high risk. The vaccine is usually effective against three or four types of influenza. It is usually well tolerated. A vaccine made for one year may not be useful in the following year, since the virus evolves rapidly. Antiviral drugs such as the neuraminidase inhibitor oseltamivir, among others, have been used to treat influenza. Their benefits in those who are otherwise healthy do not appear to be greater than their risks. No benefit has been found in those with other health problems.
Influenza spreads around the world in a yearly outbreak, resulting in about three to five million cases of severe illness and about 250,000 to 500,000 deaths. In the Northern and Southern parts of the world, outbreaks occur mainly in winter while in areas around the equator outbreaks may occur at any time of the year. Death occurs mostly in the young, the old and those with other health problems. Larger outbreaks known as pandemics are less frequent. In the 20th century, three influenza pandemics occurred: Spanish influenza in 1918 (~50 million deaths), Asian influenza in 1957 (two million deaths), and Hong Kong influenza in 1968 (one million deaths). The World Health Organization declared an outbreak of a new type of influenza A/H1N1 to be a pandemic in June 2009. Influenza may also affect other animals, including pigs, horses and birds.
Stasis papillomatosis is a disease characterized by chronic congestion of the extremities, with blood circulation interrupted in a specific area of the body. A consequence of this congestion and inflammation is long-term lymphatic obstruction. It is also typically characterized by the appearance of numerous papules. Injuries can range from small to large plates composed of brown or pink, smooth or hyperkeratotic papules. The most typical areas where injuries occur are the back of the feet, the toes, the legs, and the area around a venous ulcer formed in the extremities, although the latter is the rarest of all. These injuries include pachydermia (thickening of the skin), lymphedema, lymphomastic verrucusis and elephantosis verracosa. The disease can be either localized or generalized; the localized form makes up 78% of cases. Treatment includes surgical and pharmaceutical intervention; indications for partial removal include advanced fibrotic lymphedema and elephantiasis. Despite the existence of these treatments, chronic venous edema, which is a derivation of stasis papillomatosis, is only partially reversible. The skin is also affected and its partial removal may mean that the skin and the subcutaneous tissue are excised. A side effect of the procedure is the destruction of existing cutaneous lymphatic vessels. It also risks papillomatosis, skin necrosis and edema exacerbation.
All etiologies lead to local dermal lymphostasis pathogenesis. A maximum variation was observed after the resection of block subcutaneous tissue in patients suffering from congenital lymphedema. Signals that the current condition are different, either in the dermis or in the subcutaneous area. In dermis, principal signs found are precollectors initial nodes, injection tank, the reticular distribution, cutaneous reflexes, and lymphatic cysts. On other hand in the subcutaneous area principal signs are; collectors, thinning, ectatic, tortuous, rest offs, reflux dermal, sclerosis, calcifications.
Pityriasis alba is a common skin condition mostly occurring in children and usually seen as dry, fine-scaled, pale patches on the face. It is self-limiting and usually only requires use of moisturizer creams.
The condition is so named for the fine scaly appearance initially present (pityriasis) and the pallor of the patches that develop (while "alba" is Latin for white, the patches in this condition are not totally depigmented).
Gout can present in multiple ways, although the most usual is a recurrent attack of acute inflammatory arthritis (a red, tender, hot, swollen joint). The metatarsal-phalangeal joint at the base of the big toe is affected most often, accounting for half of cases. Other joints, such as the heels, knees, wrists, and fingers, may also be affected. Joint pain usually begins over 2–4 hours and during the night. This is mainly due to lower body temperature. Other symptoms may rarely occur along with the joint pain, including fatigue and a high fever.
Long-standing elevated uric acid levels (hyperuricemia) may result in other symptoms, including hard, painless deposits of uric acid crystals known as tophi. Extensive tophi may lead to chronic arthritis due to bone erosion. Elevated levels of uric acid may also lead to crystals precipitating in the kidneys, resulting in stone formation and subsequent urate nephropathy.
Characteristic injuries associated with AHT include retinal bleeds, multiple fractures of the long bones, and subdural hematomas (bleeding in the brain). These signs have evolved through the years as the accepted and recognized signs of child abuse. Medical professionals strongly suspect shaking as the cause of injuries when a young child presents with retinal bleed, fractures, soft tissue injuries or subdural hematoma, that cannot be explained by accidental trauma or other medical conditions.
Retinal bleeds occur in around 85% of AHT cases; the type of retinal bleeds are particularly characteristic of this condition, making the finding useful in establishing the diagnosis. While there are many other causes of retinal bleeds besides AHT, there are usually additional findings (eyes or systemic) which make the alternative diagnoses apparent.
Fractures of the vertebrae, long bones, and ribs may also be associated with AHT. Dr. John Caffey reported in 1972 that metaphyseal avulsions (small fragments of bone had been torn off where the periosteum covering the bone and the cortical bone are tightly bound together) and "bones on both the proximal and distal sides of a single joint are affected, especially at the knee".
People after AHT may display irritability, failure to thrive, alterations in eating patterns, lethargy, vomiting, seizures, bulging or tense fontanels (the soft spots on a baby's head), increased size of the head, altered breathing, and dilated pupils.
If symptoms of histoplasmosis infection occur, they will start within 3 to 17 days after exposure; the average is 12–14 days. Most affected individuals have clinically silent manifestations and show no apparent ill effects. The acute phase of histoplasmosis is characterized by non-specific respiratory symptoms, often cough or flu-like. Chest X-ray findings are normal in 40–70% of cases. Chronic histoplasmosis cases can resemble tuberculosis; disseminated histoplasmosis affects multiple organ systems and is fatal unless treated.
While histoplasmosis is the most common cause of mediastinitis, this remains a relatively rare disease. Severe infections can cause hepatosplenomegaly, lymphadenopathy, and adrenal enlargement. Lesions have a tendency to calcify as they heal.
Presumed ocular histoplasmosis syndrome (POHS) causes chorioretinitis, where the choroid and retina of the eyes are scarred, resulting in a loss of vision not unlike macular degeneration. Despite its name, the relationship to "Histoplasma" is controversial. Distinct from POHS, acute ocular histoplasmosis may rarely occur in immunodeficiency.